Pro-inflammatory cytokines in patients with low back pain: A comparative study

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"autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Maroua Slouma, Lobna Kharrat, Aymen Tezegdenti, Leila Metoui, Ezzeddine Ghazouani, Rim Dhahri, Imen Gharsallah, Bassem Louzir" "autores" => array:8 [ 0 => array:3 [ "nombre" => "Maroua" "apellidos" => "Slouma" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 1 => array:4 [ "nombre" => "Lobna" "apellidos" => "Kharrat" "email" => array:1 [ 0 => "kharratlobna1992@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Aymen" "apellidos" => "Tezegdenti" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ 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"aff0015" ] 1 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Rheumatology, Military Hospital, Tunis, Tunisia" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Immunology, Military Hospital, Tunis, Tunisia" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Tunis El Manar University, Tunisia" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Department of Internal Medicine, Military Hospital, Tunis, Tunisia" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Citoquinas proinflamatorias en pacientes con dolor lumbar: un estudio comparativo" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1240 "Ancho" => 1245 "Tamanyo" => 54127 ] ] "descripcion" => array:1 [ "en" => "Receiver operating characteristic curve (ROC) showing the discriminative value of IL-8 between LBP and pain-free controls." ] ] ] "textoCompleto" => "IntroductionLow back pain (LBP) is a global healthcare concern. Non-specific LBP is the most common form.<a class="elsevierStyleCrossRef" href="#bib0155">1</a> It can be due to several diseases, such as disk disease (intervertebral disk degeneration (IDD) or lumbar disk herniation (LDH)), facet joint osteoarthritis, and spinal stenosis.<a class="elsevierStyleCrossRef" href="#bib0160">2</a>Non-specific LBP is a very common disease that affects 70 to 90% of general population.<a class="elsevierStyleCrossRef" href="#bib0165">3</a> Fifteen per cent of work absenteeism is caused by LBP.<a class="elsevierStyleCrossRef" href="#bib0165">3</a> It can be responsible for disability and restricted lumbar range of motion.<a class="elsevierStyleCrossRef" href="#bib0170">4</a>Thus, a better understanding of the pathophysiology of low back pain is necessary to ensure appropriate care for this potentially disabling disease.Despite its frequency, LBP's diagnosis remains sometimes difficult and mainly based on the elimination of other spinal diseases.<a class="elsevierStyleCrossRef" href="#bib0175">5</a> LBP pathophysiology is, up to now, unclear.There are controversial results regarding the role of pro-inflammatory cytokines such as interleukin (IL-)6, IL-8, IL-17, IL-23, IL-22, and Tumor necrosis factor (TNFα) in the physiopathology of non-specific LBP<a class="elsevierStyleCrossRefs" href="#bib0175">5,6</a> and its recurrence.<a class="elsevierStyleCrossRef" href="#bib0185">7</a>Besides, several studies showed that pro-inflammatory cytokines contribute to the pathogenesis of IDD and associated pain mechanisms.<a class="elsevierStyleCrossRefs" href="#bib0190">8,9</a>This study aimed to compare the value of these pro-inflammatory cytokines between patients with non-specific LBP and pain-free controls.Material and methodsPatientsWe conducted a case–control study from September 2019 to December 2020 including 106 participants:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-G1: 46 consecutive patients with non-specific LBP recruited from the outpatient clinic of the rheumatology department.</li><li class="elsevierStyleListItem" id="lsti0010">-G0: 60 pain-free controls recruited from different departments in the Military hospital of Tunis.</li></ul>Inclusion criteriaWere included in this study patients with chronic non-specific LBP lasting>3 months.Only patients with magnetic resonance imaging (MRI) showing single LDH or IDD were included in the study. The interpretation of MRIs was performed by a trained radiologist.Exclusion criteriaNon-inclusions criteria for the two groups were: history of neoplasia, asthma, infections, chronic inflammatory bowel disease, psoriasis, auto-immune disease (rheumatoid arthritis, systemic lupus erythematosus), or steroids treatment.Patients with LBP treated with surgery were not included.Were excluded patients with LBP due to spondyloarthritis, infectious spondylodiscitis, or metastasis.Clinical assessmentWe collected demographic and clinical data, including age, gender, age at disease onset, LBP duration, radicular pain, and therapeutic management.The pain degree was assessed using the Visual Analogic Scale (VAS). The VAS varied from “no pain” to “worst imaginable pain” (0–100mm).Lumbar spine mobility was evaluated using Schober's test.<a class="elsevierStyleCrossRef" href="#bib0200">10</a> A restricted lumbar motion was defined as a difference between the measurements in erect and flexion positions lower than 5cm.Cytokine's measurementThe IL-6, IL-8, IL-17, IL-23, IL-22, and (TNFα) were measured. The blood samples were collected, centrifuged, and frozen at −80°C. IL-6, IL-8, and TNFα were measured using the chemiluminescence method, whereas IL-17, IL-22, and IL-23 levels were measured using the ELISA (Enzyme-linked Immunosorbent Assay).Statistical analysisStatistical analysis was performed using the Statistical Package for Social Sciences (SPSS) software version 25. We used descriptive statistics to identify the characteristics of the study population. Results were expressed as the mean±standard deviation (SD).Continuous variables were compared using t-tests for normally distributed variables and the Mann–Whitney U test for non-normally distributed groups. Correlations were tested using the Pearson or Spearman correlation test, depending on data distribution. p-Value<0.05 was considered statistically significant.To assess the normality of data, we used the Kolmogorov–Smirnov test. Receiver operating characteristic (ROC) curves were used for each cytokine to evaluate their ability to discriminate patients with non-specific LBP from pain-free controls.Ethical considerationThis study was approved by eight members of the ethics committee of the hospital in May 2019.All participants were requested to read and sign an informed consent form explaining the aim and process of the study.ResultClinical and epidemiological characteristics of patientsAll patients were Caucasian. There were 36 men in G1 and 46 in G0. The mean age was 43.17±8.7 years in G1 and 39.56±9.95 years in G0. The mean body mass index (BMI) was 27.31±3.47kg/m2.Clinical characteristics of patients with non-specific LBP are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The mean age at the onset of LBP was 38.43±9.75 years.The mean duration of LBP was 4.72±3.03 years.Radicular pain was found in 37 cases with a VAS of 3.03±2.5mm. The magnetic resonance imaging was performed for all patients (G1), showing LDH and IDD in 54.3% (n=25) and 45.7% of cases (n=21), respectively.Spine limitation was found in 15 cases.Comparison of cytokinesThe IL-8 was higher in G1 (18.84±44.64 versus 4.34±1.23pg/mL, p:0.033). There was no significant difference between the two groups regarding the other cytokines. There were no differences between patients with LDH or IDD regarding IL-8 (23.91±62.64 versus 14.95±20.64pg/mL, p:0.29) and TNFα (19.8±46.7 versus 7.2±1.3pg/mL, p:0.75).IL-17 was higher in patients with restricted lumbar spine mobility (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Correlations between clinical parameters and cytokinesAs shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>, a correlation was found between: IL-8 and TNFα (r:0.942, p<10−3), IL-8 and IL-6 (r:0.490, p: 0.011), and IL-17 and IL-6 (r:0.945, p<10−3). IL-8 levels correlated also with VASRadicular-pain (r:0.297, p:0.047).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Discriminative value of pro-inflammatory cytokines between patients with LBP and pain-free controlsThe IL-8 could differentiate patients in G1 from G0 with a cutoff of 4.5pg/mL. The area under the curve was good (0.917) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The sensitivity and specificity were 91.3% and 90%, respectively.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>DiscussionWe attempted to study pro-inflammatory cytokines, including IL-6, IL-8, IL-17, IL-23, IL-22, and TNFα, in patients with chronic LBP. We found that IL-8 was higher in patients with non-specific LBP, and it was able to differentiate patients with LBP from pain-free controls with a cutoff of 4.5pg/mL.Several studies have analyzed the role of cytokines in LBP, with variable results but with a predominance of pro-inflammatory cytokines, indicating the role of inflammatory process in causing disk damage.In a study including 127 patients with lumbar radicular pain due to LDH, the authors demonstrated that chronic pain patients had increased serum levels of IL-8 at 6 weeks and 12 months after LDH.<a class="elsevierStyleCrossRef" href="#bib0205">11</a> These findings suggest that IL-8 may contribute to the development of chronic pain after LDH.<a class="elsevierStyleCrossRef" href="#bib0205">11</a> Moreover, it has been proven in animal models that IL-8 was implicated in the pathophysiology of neuropathic pain.<a class="elsevierStyleCrossRef" href="#bib0210">12</a>Likewise, Wang et al. demonstrated that IL-8 and TNFα levels were higher in patients with LBP and sciatica than healthy controls. They also found that TNFα correlated with Oswestry Disability Index (r:0.629, p:0.001)<a class="elsevierStyleCrossRef" href="#bib0215">13</a> which is a patient reported outcomes questionnaire used to assess functional disability in back pain patients.<a class="elsevierStyleCrossRef" href="#bib0220">14</a>This finding suggests that pro-inflammatory cytokines contribute to the generation and persistence of pain.In a study including 155 women with acute LBP, an association was found between TNFα elevation and pain severity. TNFα was also associated with disability.<a class="elsevierStyleCrossRef" href="#bib0225">15</a>In a longitudinal study including 120 patients with LBP matched to a healthy control group, the TNFα was positive in 57.6% LBP patients versus 12.3% of controls at the beginning of the study. The TNFα levels decreased after 10 days of multidisciplinary therapy, then remained constantly high in LBP patients. Nevertheless, no significant correlation was found between TNFα levels and pain.<a class="elsevierStyleCrossRef" href="#bib0230">16</a>Krock et al. found that IL-8 levels in the spinal fluid were higher in patients with chronic LBP due to IDD than those with IDD without pain. The authors highlighted the effect of blocking IL-8 receptor signaling on reducing LBP behaviors and disk inflammation in a mouse model.<a class="elsevierStyleCrossRef" href="#bib0235">17</a>Karppinen et al. assessed the serum biomarkers in chronic LBP patients with lumbar Modic change. They found that IL-8 and TNFα were lower among these patients than pain-free controls.<a class="elsevierStyleCrossRef" href="#bib0240">18</a>Schroeder et al. showed that TNFα was higher in patients with intervertebral discs with type II Modic changes.<a class="elsevierStyleCrossRef" href="#bib0245">19</a>These findings suggest the possible pathophysiological role of IL-8 and TNFα in LBP and radicular pain due to IDD or LDH. However, their role in LBP related to vertebral bone marrow lesions such as Modic change remains unclear and needs to be more closely assessed.<a class="elsevierStyleCrossRef" href="#bib0245">19</a>In our study, a strong correlation was found between IL-8 and TNFα. This correlation (IL-8/TNFα r:0.35; p=0.003) was also noted in the study of Licciardone et al., highlighting the link between pro-inflammatory cytokines in non-specific LBP.<a class="elsevierStyleCrossRef" href="#bib0250">20</a>Zhang Y et al. demonstrated that intervertebral disk cells could produce IL-1, IL-7, and IL-8.<a class="elsevierStyleCrossRef" href="#bib0255">21</a> They suggested that these cytokines mediate discogenic pain by stimulating nerve endings in intervertebral disk and contribute to the persistence of this pain by diffusing these cytokines to nearby tissues.<a class="elsevierStyleCrossRef" href="#bib0255">21</a>IL-8 can also promote angiogenesis and attract neutrophils in pathological sites.<a class="elsevierStyleCrossRef" href="#bib0260">22</a>Besides, IL-8 can promote microglial activation in the lumbar disk herniation rate model.<a class="elsevierStyleCrossRef" href="#bib0265">23</a> Chronic pain maintenance can be explained by delayed IL-8 upregulation in the spinal cord and the dorsal root ganglion.<a class="elsevierStyleCrossRef" href="#bib0265">23</a>These findings suggest that IL-8 inhibition may be a potential therapy for chronic low back pain.Several studies emphasize the role of IL-17 in the pathophysiology of IDD and demonstrate that IL-17 is an important regulator of inflammation in disk diseases.<a class="elsevierStyleCrossRefs" href="#bib0270">24,25</a>Besides, IL-17 may contribute to the pain genesis in patients with LBP. Cheng et al. found that VAS pain score was positively correlated with IL-17 concentration (r=0.458, p=0.007) in patients with LBP. IL-17 levels were also higher in patients with ruptured lumbar disk (12.13±3.62pg/ml) than those with non-ruptured lumbar discs (5.06±3.78pg/ml, p=0.003) and healthy controls (1.31±0.77pg/ml, p<0.001).<a class="elsevierStyleCrossRef" href="#bib0190">8</a>In our study, IL-17 was significantly higher in patients with spine limitations.A correlation was found between IL-6 and both IL-8 and IL-17. In a study assessing IL-6 expression in paravertebral muscle, annulus fibrosus, and nucleus pulposus biopsies, the IL-6 was found in all lumbar disk hernias biopsies but not in controls. This result suggests that the lumbar disk hernia is associated with a local inflammatory process. Nevertheless, there was no correlation between IL-6 expression and VAS scores.<a class="elsevierStyleCrossRef" href="#bib0280">26</a>Notably, some authors highlighted that elevated pro-inflammatory cytokines levels in LBP were due to adipocytes stimulation in overweight and obese patients.<a class="elsevierStyleCrossRef" href="#bib0285">27</a> In our study there was no correlation between cytokines levels and BMI. Pro-inflammatory cytokines like IL-6, IL-8 and TNFα correlated to BMI in subjects without LBP.<a class="elsevierStyleCrossRefs" href="#bib0290">28–30</a> To our knowledge, the correlation between pro-inflammatory cytokines was not assessed in LBP patients.To our knowledge, this study is the first to determine an IL-8 threshold to distinguish LBP patients from healthy controls. The results of our study are encouraging. However, some limitations must be considered, notably the small number of patients with LBP.ConclusionIL-8 seemed to be the most important pro-inflammatory cytokine in patients with disk-disease, as it was significantly higher in patients with LBP.IL-8 correlated with VAS, highlighting the role of this cytokine in the development of chronic pain in patients with disk disease.TNFα concentrations correlated with IL-8 and IL-17 levels were higher in patients with restricted lumbar pain, suggesting that these cytokines might play a role in the pathophysiology of disk disease. These findings could potentially be used by future studies to develop new LBP therapeutic strategies.Authors’ contributions<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">-Dr. Maroua SLOUMA: Methodology and Writing – review & editing</li><li class="elsevierStyleListItem" id="lsti0020">-Dr. Lobna KHARRAT: Roles/Writing – original draft</li><li class="elsevierStyleListItem" id="lsti0025">-Dr. Aymen TEZEGDENTI: data curation and funding acquisition</li><li class="elsevierStyleListItem" id="lsti0030">-Dr. Rim DHAHRI: formal analysis</li><li class="elsevierStyleListItem" id="lsti0035">-Dr Ezzeddine GHAZOUANI: project administration</li><li class="elsevierStyleListItem" id="lsti0040">-Dr. Leila METOUI: conceptualisation</li><li class="elsevierStyleListItem" id="lsti0045">-Dr. Imen GHARSALLAH: visualization</li><li class="elsevierStyleListItem" id="lsti0050">-Dr. Bassem LOUZIR: visualization and validation</li></ul>Availability of data and materialThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.Code availability (software application or custom code)Not applicable.Ethics approvalThis study was approved by the ethics committee of the Hospital.Consent to participateA consent has been signed by each patient.FundingThe authors declare that they have no funding for the research.Conflict of interestNone." "textoCompletoSecciones" => array:1 [ "secciones" => array:18 [ 0 => array:3 [ "identificador" => "xres1893819" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1638524" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1893818" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1638523" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Inclusion criteria" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Exclusion criteria" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Clinical assessment" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Cytokine's measurement" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Ethical consideration" ] ] ] 6 => array:3 [ "identificador" => "sec0050" "titulo" => "Result" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Clinical and epidemiological characteristics of patients" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Comparison of cytokines" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "Correlations between clinical parameters and cytokines" ] 3 => array:2 [ "identificador" => "sec0070" "titulo" => "Discriminative value of pro-inflammatory cytokines between patients with LBP and pain-free controls" ] ] ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Authors’ contributions" ] 10 => array:2 [ "identificador" => "sec0090" "titulo" => "Availability of data and material" ] 11 => array:2 [ "identificador" => "sec0095" "titulo" => "Code availability (software application or custom code)" ] 12 => array:2 [ "identificador" => "sec0100" "titulo" => "Ethics approval" ] 13 => array:2 [ "identificador" => "sec0105" "titulo" => "Consent to participate" ] 14 => array:2 [ "identificador" => "sec0110" "titulo" => "Funding" ] 15 => array:2 [ "identificador" => "sec0115" "titulo" => "Conflict of interest" ] 16 => array:2 [ "identificador" => "xack665188" "titulo" => "Acknowledgements" ] 17 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-03-29" "fechaAceptado" => "2022-07-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1638524" "palabras" => array:6 [ 0 => "Back pain" 1 => "Disk herniation" 2 => "Cytokine" 3 => "Interleukin-8" 4 => "Tumor necrosis factor α" 5 => "Interleukin-17" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1638523" "palabras" => array:6 [ 0 => "Dolor de espalda" 1 => "Hernia discal" 2 => "Citoquina" 3 => "Interleucina 8" 4 => "Factor de necrosis tumoral α" 5 => "Interleucina 17" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Introduction and objectivesThere are controversial results regarding the value of serum IL-8 and TNFα in patients with non-specific low back pain.This study aimed to compare pro-inflammatory cytokines between patients with non-specific back pain and pain-free controls. Materials and methodsWe conducted a case–control study including 106 participants: 46 patients with chronic non-specific low back pain (G1) and 60 pain-free controls (G0). The interleukin (IL-)6, IL-8, IL-17, IL-23, IL-22, and Tumor necrosis factor α (TNFα) were measured. We collected demographic and clinical data, including age, gender, low back pain duration and radicular pain. The pain degree was assessed using the Visual Analogic Scale. ResultsThe mean age was 43.17±8.7 years in G1. Radicular pain was found in 37 cases with a Visual Analogic Scale of 3.03±2.5mm. The magnetic resonance imaging was performed in (G1), showing disk herniation and degenerative disk disease in 54.3% (n=25) and 45.7% of cases (n=21), respectively. The IL-8 was higher in G1 (18.84±44.64 versus 4.34±1.23pg/mL, p:0.033). IL-8 levels correlated with TNFα (0.942, p<10–3), IL-6 (0.490, p=0.011) and Visual Analogic ScaleRadicular-pain (r:0.297, p:0.047).IL-17 was higher in patients with restricted lumbar spine mobility (9.64±20.77 versus 1.19±2.54pg/mL, p:0.014). ConclusionsOur results provide evidence that IL-8 and TNFα play a role in low back pain and radicular pain due to disk degeneration or herniation. These findings could potentially be used by future studies to develop new non-specific low back pain therapeutic strategies." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "Introducción y objetivosExisten resultados controvertidos en cuanto al valor de la interleucina (IL) 8 y el factor de necrosis tumoral α (TNFα) séricos en pacientes con lumbalgia inespecífica.Este estudio tuvo como objetivo comparar las citoquinas proinflamatorias entre pacientes con dolor de espalda inespecífico y controles sin dolor. Materiales y métodosRealizamos un estudio de casos y controles que incluyó a 106 participantes: 46 pacientes con dolor lumbar crónico inespecífico (G1) y 60 controles sin dolor (G0). Se midieron las IL-6, IL-8, IL-17, IL-23, IL-22 y el TNFα. Recopilamos datos demográficos y clínicos, incluidos la edad, el sexo, la duración del dolor lumbar y el dolor radicular. El grado de dolor se evaluó mediante la escala analógica visual. ResultadosLa edad media fue de 43,17±8,7 años en G1. Se encontró dolor radicular en 37 casos con una escala analógica visual de 3,03±2,5mm. La resonancia magnética se realizó en G1, mostrando hernia discal y enfermedad discal degenerativa en el 54,3% (n=25) y el 45,7% de los casos (n=21), respectivamente. La IL-8 fue mayor en G1 (18,84±44,64 versus 4,34±1,23pg/ml, p=0,033). Los niveles de IL-8 se correlacionaron con TNFα (0,942, p<10−3), IL-6 (0,490, p=0,011) y escala visual analógicadolor radicular (r=0,297, p=0,047).IL-17 fue mayor en pacientes con movilidad restringida de la columna lumbar (9,64±20,77 versus 1,19±2,54pg/ml, p=0,014). ConclusionesNuestros resultados proporcionan evidencia de que la IL-8 y el TNFα juegan un papel en el dolor lumbar y en el dolor radicular debido a la degeneración o a hernia discal. Estos hallazgos podrían potencialmente ser utilizados por estudios futuros para desarrollar nuevas estrategias terapéuticas no específicas para el dolor lumbar." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1240 "Ancho" => 1245 "Tamanyo" => 54127 ] ] "descripcion" => array:1 [ "en" => "Receiver operating characteristic curve (ROC) showing the discriminative value of IL-8 between LBP and pain-free controls." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "LBP: low back pain, VAS: Visual Analog Scale, MRI: magnetic resonance imaging." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age, mean±SD years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43.17±8.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age at the onset of LBP, mean±SD years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38.43±9.57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Body mass index, mean±SD kg/m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.31±3.47 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Smoking (n (%)) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (28%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Comorbidities</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diabetes (n (%)) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypertension (n (%)) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dyslipidemia (n (%)) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (11%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical assessment</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Radicular pain (n (%)) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 (80.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VASbackpain, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.79±1.95 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VASradicularpain, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.03±2.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MRI features</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Disk herniation (n (%)) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (54.3%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Degenerative disk disease (n (%)) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (45.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3165760.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical characteristics of patients." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Values were expressed as mean±SD, p: probability value, IL: interleukin, TNFα: Tumor Necrosis Factor α." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Pain-free controls \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Patients \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Lumbar spine mobility</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Normal \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Restricted \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.17±1.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.09±1.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.83±1.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.5±1.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TNFα \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.25±2.44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.11±31.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.324 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.45±38.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.64±1.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.34±1.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18.84±44.64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.033 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21.27±53.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.84±16.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.10±1.53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.73±11.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.235 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.19±2.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.64±20.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.014 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.10±15.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.42±8.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.725 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.42±9.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.34±4.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.21 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.31±6.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.81±1.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.151 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.54±1.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.42±2.65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.53 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3165759.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Comparison of the pro-inflammatory cytokines between the two groups." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Data are presented as the r value in Pearson's correlation test." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">VASbackpain \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">VASradicularpain \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TNFα \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IL-8 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IL-17 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IL-22 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IL-23 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IL-6 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VASbackpain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.440<a class="elsevierStyleCrossRef" href="#tblfn0010">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.035 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.152 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.144 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.021 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.063 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.060 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VASradicular pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.440<a class="elsevierStyleCrossRef" href="#tblfn0010">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.192 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.297<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.040 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.050 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.166 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.096 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.149 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.311 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.201 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.386 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.174 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.048 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.255 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TNFα \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.035 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.192 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.942<a class="elsevierStyleCrossRef" href="#tblfn0015">***</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.048 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.113 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.087 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.117 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.060 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.096 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.117 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.490<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.945<a class="elsevierStyleCrossRef" href="#tblfn0010">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.328 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.332 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.152 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.297<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.942<a class="elsevierStyleCrossRef" href="#tblfn0010">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.036 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.111 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.137 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.490<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.144 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.040 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.048 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.036 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.043 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.085 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.945<a class="elsevierStyleCrossRef" href="#tblfn0010">**</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.021 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.050 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.113 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.111 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.043 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.123 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.328 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.063 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.166 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.087 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.137 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.085 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.123 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.332 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3165761.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "p<0.05." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "**" "nota" => "p<0.01." ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "***" "nota" => "p<0.001. p: probability value, IL: interleukin, TNFα: Tumor Necrosis Factor α, VAS: Visual Analog Scale, BMI: body mass index." ] ] ] "descripcion" => array:1 [ "en" => "Correlations between clinical parameter and cytokines." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-specific low back pain" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. 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Pro-inflammatory cytokines in patients with low back pain: A comparative study

Citoquinas proinflamatorias en pacientes con dolor lumbar: un estudio comparativo

Maroua Sloumaa,c, Lobna Kharrata,c,

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kharratlobna1992@gmail.com

Corresponding author.

, Aymen Tezegdentib,c, Leila Metouia,c, Ezzeddine Ghazouanib,c, Rim Dhahria,c, Imen Gharsallaha,c, Bassem Louzirc,d

a Department of Rheumatology, Military Hospital, Tunis, Tunisia

b Department of Immunology, Military Hospital, Tunis, Tunisia

c Tunis El Manar University, Tunisia

d Department of Internal Medicine, Military Hospital, Tunis, Tunisia

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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Receiver operating characteristic curve &#40;ROC&#41; showing the discriminative value of IL-8 between LBP and pain-free controls&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Low back pain &#40;LBP&#41; is a global healthcare concern&#46; Non-specific LBP is the most common form&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> It can be due to several diseases&#44; such as disk disease &#40;intervertebral disk degeneration &#40;IDD&#41; or lumbar disk herniation &#40;LDH&#41;&#41;&#44; facet joint osteoarthritis&#44; and spinal stenosis&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Non-specific LBP is a very common disease that affects 70 to 90&#37; of general population&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> Fifteen per cent of work absenteeism is caused by LBP&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> It can be responsible for disability and restricted lumbar range of motion&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Thus&#44; a better understanding of the pathophysiology of low back pain is necessary to ensure appropriate care for this potentially disabling disease&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Despite its frequency&#44; LBP&#39;s diagnosis remains sometimes difficult and mainly based on the elimination of other spinal diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> LBP pathophysiology is&#44; up to now&#44; unclear&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">There are controversial results regarding the role of pro-inflammatory cytokines such as interleukin &#40;IL-&#41;6&#44; IL-8&#44; IL-17&#44; IL-23&#44; IL-22&#44; and Tumor necrosis factor &#40;TNF&#945;&#41; in the physiopathology of non-specific LBP<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5&#44;6</span></a> and its recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Besides&#44; several studies showed that pro-inflammatory cytokines contribute to the pathogenesis of IDD and associated pain mechanisms&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">This study aimed to compare the value of these pro-inflammatory cytokines between patients with non-specific LBP and pain-free controls&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0040" class="elsevierStylePara elsevierViewall">We conducted a case&#8211;control study from September 2019 to December 2020 including 106 participants&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0045" class="elsevierStylePara elsevierViewall">G1&#58; 46 consecutive patients with non-specific LBP recruited from the outpatient clinic of the rheumatology department&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">G0&#58; 60 pain-free controls recruited from different departments in the Military hospital of Tunis&#46;</p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Inclusion criteria</span><p id="par0055" class="elsevierStylePara elsevierViewall">Were included in this study patients with chronic non-specific LBP lasting<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3 months&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Only patients with magnetic resonance imaging &#40;MRI&#41; showing single LDH or IDD were included in the study&#46; The interpretation of MRIs was performed by a trained radiologist&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Exclusion criteria</span><p id="par0065" class="elsevierStylePara elsevierViewall">Non-inclusions criteria for the two groups were&#58; history of neoplasia&#44; asthma&#44; infections&#44; chronic inflammatory bowel disease&#44; psoriasis&#44; auto-immune disease &#40;rheumatoid arthritis&#44; systemic lupus erythematosus&#41;&#44; or steroids treatment&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Patients with LBP treated with surgery were not included&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Were excluded patients with LBP due to spondyloarthritis&#44; infectious spondylodiscitis&#44; or metastasis&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Clinical assessment</span><p id="par0080" class="elsevierStylePara elsevierViewall">We collected demographic and clinical data&#44; including age&#44; gender&#44; age at disease onset&#44; LBP duration&#44; radicular pain&#44; and therapeutic management&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The pain degree was assessed using the Visual Analogic Scale &#40;VAS&#41;&#46; The VAS varied from &#8220;no pain&#8221; to &#8220;worst imaginable pain&#8221; &#40;0&#8211;100<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Lumbar spine mobility was evaluated using Schober&#39;s test&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> A restricted lumbar motion was defined as a difference between the measurements in erect and flexion positions lower than 5<span class="elsevierStyleHsp" style=""></span>cm&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Cytokine&#39;s measurement</span><p id="par0095" class="elsevierStylePara elsevierViewall">The IL-6&#44; IL-8&#44; IL-17&#44; IL-23&#44; IL-22&#44; and &#40;TNF&#945;&#41; were measured&#46; The blood samples were collected&#44; centrifuged&#44; and frozen at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; IL-6&#44; IL-8&#44; and TNF&#945; were measured using the chemiluminescence method&#44; whereas IL-17&#44; IL-22&#44; and IL-23 levels were measured using the ELISA &#40;Enzyme-linked Immunosorbent Assay&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0100" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using the Statistical Package for Social Sciences &#40;SPSS&#41; software version 25&#46; We used descriptive statistics to identify the characteristics of the study population&#46; Results were expressed as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Continuous variables were compared using <span class="elsevierStyleItalic">t</span>-tests for normally distributed variables and the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test for non-normally distributed groups&#46; Correlations were tested using the Pearson or Spearman correlation test&#44; depending on data distribution&#46; <span class="elsevierStyleItalic">p</span>-Value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered statistically significant&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">To assess the normality of data&#44; we used the Kolmogorov&#8211;Smirnov test&#46; Receiver operating characteristic &#40;ROC&#41; curves were used for each cytokine to evaluate their ability to discriminate patients with non-specific LBP from pain-free controls&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Ethical consideration</span><p id="par0115" class="elsevierStylePara elsevierViewall">This study was approved by eight members of the ethics committee of the hospital in May 2019&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">All participants were requested to read and sign an informed consent form explaining the aim and process of the study&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Result</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Clinical and epidemiological characteristics of patients</span><p id="par0125" class="elsevierStylePara elsevierViewall">All patients were Caucasian&#46; There were 36 men in G1 and 46 in G0&#46; The mean age was 43&#46;17<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;7 years in G1 and 39&#46;56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;95 years in G0&#46; The mean body mass index &#40;BMI&#41; was 27&#46;31<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;47<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Clinical characteristics of patients with non-specific LBP are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">The mean age at the onset of LBP was 38&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;75 years&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The mean duration of LBP was 4&#46;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;03 years&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Radicular pain was found in 37 cases with a VAS of 3&#46;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#46; The magnetic resonance imaging was performed for all patients &#40;G1&#41;&#44; showing LDH and IDD in 54&#46;3&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41; and 45&#46;7&#37; of cases &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#41;&#44; respectively&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Spine limitation was found in 15 cases&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Comparison of cytokines</span><p id="par0155" class="elsevierStylePara elsevierViewall">The IL-8 was higher in G1 &#40;18&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>44&#46;64 versus 4&#46;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;23<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#44; <span class="elsevierStyleItalic">p</span>&#58;0&#46;033&#41;&#46; There was no significant difference between the two groups regarding the other cytokines&#46; There were no differences between patients with LDH or IDD regarding IL-8 &#40;23&#46;91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>62&#46;64 versus 14&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#46;64<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#44; <span class="elsevierStyleItalic">p</span>&#58;0&#46;29&#41; and TNF&#945; &#40;19&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>46&#46;7 versus 7&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;3<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#44; <span class="elsevierStyleItalic">p</span>&#58;0&#46;75&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">IL-17 was higher in patients with restricted lumbar spine mobility &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Correlations between clinical parameters and cytokines</span><p id="par0165" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#44; a correlation was found between&#58; IL-8 and TNF&#945; &#40;<span class="elsevierStyleItalic">r</span>&#58;0&#46;942&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span>&#41;&#44; IL-8 and IL-6 &#40;<span class="elsevierStyleItalic">r</span>&#58;0&#46;490&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;011&#41;&#44; and IL-17 and IL-6 &#40;<span class="elsevierStyleItalic">r</span>&#58;0&#46;945&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span>&#41;&#46; IL-8 levels correlated also with VAS<span class="elsevierStyleInf">Radicular-pain</span> &#40;<span class="elsevierStyleItalic">r</span>&#58;0&#46;297&#44; <span class="elsevierStyleItalic">p</span>&#58;0&#46;047&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discriminative value of pro-inflammatory cytokines between patients with LBP and pain-free controls</span><p id="par0170" class="elsevierStylePara elsevierViewall">The IL-8 could differentiate patients in G1 from G0 with a cutoff of 4&#46;5<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#46; The area under the curve was good &#40;0&#46;917&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The sensitivity and specificity were 91&#46;3&#37; and 90&#37;&#44; respectively&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0175" class="elsevierStylePara elsevierViewall">We attempted to study pro-inflammatory cytokines&#44; including IL-6&#44; IL-8&#44; IL-17&#44; IL-23&#44; IL-22&#44; and TNF&#945;&#44; in patients with chronic LBP&#46; We found that IL-8 was higher in patients with non-specific LBP&#44; and it was able to differentiate patients with LBP from pain-free controls with a cutoff of 4&#46;5<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Several studies have analyzed the role of cytokines in LBP&#44; with variable results but with a predominance of pro-inflammatory cytokines&#44; indicating the role of inflammatory process in causing disk damage&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">In a study including 127 patients with lumbar radicular pain due to LDH&#44; the authors demonstrated that chronic pain patients had increased serum levels of IL-8 at 6 weeks and 12 months after LDH&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> These findings suggest that IL-8 may contribute to the development of chronic pain after LDH&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> Moreover&#44; it has been proven in animal models that IL-8 was implicated in the pathophysiology of neuropathic pain&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Likewise&#44; Wang et al&#46; demonstrated that IL-8 and TNF&#945; levels were higher in patients with LBP and sciatica than healthy controls&#46; They also found that TNF&#945; correlated with Oswestry Disability Index &#40;<span class="elsevierStyleItalic">r</span>&#58;0&#46;629&#44; <span class="elsevierStyleItalic">p</span>&#58;0&#46;001&#41;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> which is a patient reported outcomes questionnaire used to assess functional disability in back pain patients&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">This finding suggests that pro-inflammatory cytokines contribute to the generation and persistence of pain&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">In a study including 155 women with acute LBP&#44; an association was found between TNF&#945; elevation and pain severity&#46; TNF&#945; was also associated with disability&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">In a longitudinal study including 120 patients with LBP matched to a healthy control group&#44; the TNF&#945; was positive in 57&#46;6&#37; LBP patients versus 12&#46;3&#37; of controls at the beginning of the study&#46; The TNF&#945; levels decreased after 10 days of multidisciplinary therapy&#44; then remained constantly high in LBP patients&#46; Nevertheless&#44; no significant correlation was found between TNF&#945; levels and pain&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">Krock et al&#46; found that IL-8 levels in the spinal fluid were higher in patients with chronic LBP due to IDD than those with IDD without pain&#46; The authors highlighted the effect of blocking IL-8 receptor signaling on reducing LBP behaviors and disk inflammation in a mouse model&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Karppinen et al&#46; assessed the serum biomarkers in chronic LBP patients with lumbar Modic change&#46; They found that IL-8 and TNF&#945; were lower among these patients than pain-free controls&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Schroeder et al&#46; showed that TNF&#945; was higher in patients with intervertebral discs with type II Modic changes&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">These findings suggest the possible pathophysiological role of IL-8 and TNF&#945; in LBP and radicular pain due to IDD or LDH&#46; However&#44; their role in LBP related to vertebral bone marrow lesions such as Modic change remains unclear and needs to be more closely assessed&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">In our study&#44; a strong correlation was found between IL-8 and TNF&#945;&#46; This correlation &#40;IL-8&#47;TNF&#945; <span class="elsevierStyleItalic">r</span>&#58;0&#46;35&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41; was also noted in the study of Licciardone et al&#46;&#44; highlighting the link between pro-inflammatory cytokines in non-specific LBP&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Zhang Y et al&#46; demonstrated that intervertebral disk cells could produce IL-1&#44; IL-7&#44; and IL-8&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> They suggested that these cytokines mediate discogenic pain by stimulating nerve endings in intervertebral disk and contribute to the persistence of this pain by diffusing these cytokines to nearby tissues&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">IL-8 can also promote angiogenesis and attract neutrophils in pathological sites&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">Besides&#44; IL-8 can promote microglial activation in the lumbar disk herniation rate model&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> Chronic pain maintenance can be explained by delayed IL-8 upregulation in the spinal cord and the dorsal root ganglion&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">These findings suggest that IL-8 inhibition may be a potential therapy for chronic low back pain&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Several studies emphasize the role of IL-17 in the pathophysiology of IDD and demonstrate that IL-17 is an important regulator of inflammation in disk diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">24&#44;25</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Besides&#44; IL-17 may contribute to the pain genesis in patients with LBP&#46; Cheng et al&#46; found that VAS pain score was positively correlated with IL-17 concentration &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;458&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#41; in patients with LBP&#46; IL-17 levels were also higher in patients with ruptured lumbar disk &#40;12&#46;13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;62<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; than those with non-ruptured lumbar discs &#40;5&#46;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;78<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41; and healthy controls &#40;1&#46;31<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;77<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">In our study&#44; IL-17 was significantly higher in patients with spine limitations&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">A correlation was found between IL-6 and both IL-8 and IL-17&#46; In a study assessing IL-6 expression in paravertebral muscle&#44; annulus fibrosus&#44; and nucleus pulposus biopsies&#44; the IL-6 was found in all lumbar disk hernias biopsies but not in controls&#46; This result suggests that the lumbar disk hernia is associated with a local inflammatory process&#46; Nevertheless&#44; there was no correlation between IL-6 expression and VAS scores&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">Notably&#44; some authors highlighted that elevated pro-inflammatory cytokines levels in LBP were due to adipocytes stimulation in overweight and obese patients&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> In our study there was no correlation between cytokines levels and BMI&#46; Pro-inflammatory cytokines like IL-6&#44; IL-8 and TNF&#945; correlated to BMI in subjects without LBP&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">28&#8211;30</span></a> To our knowledge&#44; the correlation between pro-inflammatory cytokines was not assessed in LBP patients&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">To our knowledge&#44; this study is the first to determine an IL-8 threshold to distinguish LBP patients from healthy controls&#46; The results of our study are encouraging&#46; However&#44; some limitations must be considered&#44; notably the small number of patients with LBP&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusion</span><p id="par0285" class="elsevierStylePara elsevierViewall">IL-8 seemed to be the most important pro-inflammatory cytokine in patients with disk-disease&#44; as it was significantly higher in patients with LBP&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">IL-8 correlated with VAS&#44; highlighting the role of this cytokine in the development of chronic pain in patients with disk disease&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">TNF&#945; concentrations correlated with IL-8 and IL-17 levels were higher in patients with restricted lumbar pain&#44; suggesting that these cytokines might play a role in the pathophysiology of disk disease&#46; These findings could potentially be used by future studies to develop new LBP therapeutic strategies&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Authors&#8217; contributions</span><p id="par0300" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0305" class="elsevierStylePara elsevierViewall">Dr&#46; Maroua SLOUMA&#58; Methodology and Writing &#8211; review &#38; editing</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0310" class="elsevierStylePara elsevierViewall">Dr&#46; Lobna KHARRAT&#58; Roles&#47;Writing &#8211; original draft</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0315" class="elsevierStylePara elsevierViewall">Dr&#46; Aymen TEZEGDENTI&#58; data curation and funding acquisition</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0320" class="elsevierStylePara elsevierViewall">Dr&#46; Rim DHAHRI&#58; formal analysis</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0325" class="elsevierStylePara elsevierViewall">Dr Ezzeddine GHAZOUANI&#58; project administration</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0330" class="elsevierStylePara elsevierViewall">Dr&#46; Leila METOUI&#58; conceptualisation</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0335" class="elsevierStylePara elsevierViewall">Dr&#46; Imen GHARSALLAH&#58; visualization</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0340" class="elsevierStylePara elsevierViewall">Dr&#46; Bassem LOUZIR&#58; visualization and validation</p></li></ul></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Availability of data and material</span><p id="par0345" class="elsevierStylePara elsevierViewall">The datasets used and&#47;or analyzed during the current study are available from the corresponding author on reasonable request&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Code availability &#40;software application or custom code&#41;</span><p id="par0350" class="elsevierStylePara elsevierViewall">Not applicable&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Ethics approval</span><p id="par0355" class="elsevierStylePara elsevierViewall">This study was approved by the ethics committee of the Hospital&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Consent to participate</span><p id="par0360" class="elsevierStylePara elsevierViewall">A consent has been signed by each patient&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Funding</span><p id="par0365" class="elsevierStylePara elsevierViewall">The authors declare that they have no funding for the research&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Conflict of interest</span><p id="par0370" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">There are controversial results regarding the value of serum IL-8 and TNF&#945; in patients with non-specific low back pain&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This study aimed to compare pro-inflammatory cytokines between patients with non-specific back pain and pain-free controls&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We conducted a case&#8211;control study including 106 participants&#58; 46 patients with chronic non-specific low back pain &#40;G1&#41; and 60 pain-free controls &#40;G0&#41;&#46; The interleukin &#40;IL-&#41;6&#44; IL-8&#44; IL-17&#44; IL-23&#44; IL-22&#44; and Tumor necrosis factor &#945; &#40;TNF&#945;&#41; were measured&#46; We collected demographic and clinical data&#44; including age&#44; gender&#44; low back pain duration and radicular pain&#46; The pain degree was assessed using the Visual Analogic Scale&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The mean age was 43&#46;17<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;7 years in G1&#46; Radicular pain was found in 37 cases with a Visual Analogic Scale of 3&#46;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#46; The magnetic resonance imaging was performed in &#40;G1&#41;&#44; showing disk herniation and degenerative disk disease in 54&#46;3&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41; and 45&#46;7&#37; of cases &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#41;&#44; respectively&#46; The IL-8 was higher in G1 &#40;18&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>44&#46;64 versus 4&#46;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;23<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#44; <span class="elsevierStyleItalic">p</span>&#58;0&#46;033&#41;&#46; IL-8 levels correlated with TNF&#945; &#40;0&#46;942&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10&#8211;3&#41;&#44; IL-6 &#40;0&#46;490&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;011&#41; and Visual Analogic Scale<span class="elsevierStyleInf">Radicular-pain</span> &#40;<span class="elsevierStyleItalic">r</span>&#58;0&#46;297&#44; <span class="elsevierStyleItalic">p</span>&#58;0&#46;047&#41;&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">IL-17 was higher in patients with restricted lumbar spine mobility &#40;9&#46;64<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#46;77 versus 1&#46;19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;54<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#44; <span class="elsevierStyleItalic">p</span>&#58;0&#46;014&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Our results provide evidence that IL-8 and TNF&#945; play a role in low back pain and radicular pain due to disk degeneration or herniation&#46; These findings could potentially be used by future studies to develop new non-specific low back pain therapeutic strategies&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Existen resultados controvertidos en cuanto al valor de la interleucina &#40;IL&#41; 8 y el factor de necrosis tumoral &#945; &#40;TNF&#945;&#41; s&#233;ricos en pacientes con lumbalgia inespec&#237;fica&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este estudio tuvo como objetivo comparar las citoquinas proinflamatorias entre pacientes con dolor de espalda inespec&#237;fico y controles sin dolor&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materiales y m&#233;todos</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Realizamos un estudio de casos y controles que incluy&#243; a 106 participantes&#58; 46 pacientes con dolor lumbar cr&#243;nico inespec&#237;fico &#40;G1&#41; y 60 controles sin dolor &#40;G0&#41;&#46; Se midieron las IL-6&#44; IL-8&#44; IL-17&#44; IL-23&#44; IL-22 y el TNF&#945;&#46; Recopilamos datos demogr&#225;ficos y cl&#237;nicos&#44; incluidos la edad&#44; el sexo&#44; la duraci&#243;n del dolor lumbar y el dolor radicular&#46; El grado de dolor se evalu&#243; mediante la escala anal&#243;gica visual&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La edad media fue de 43&#44;17<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#44;7 a&#241;os en G1&#46; Se encontr&#243; dolor radicular en 37 casos con una escala anal&#243;gica visual de 3&#44;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;5<span class="elsevierStyleHsp" style=""></span>mm&#46; La resonancia magn&#233;tica se realiz&#243; en G1&#44; mostrando hernia discal y enfermedad discal degenerativa en el 54&#44;3&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41; y el 45&#44;7&#37; de los casos &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#41;&#44; respectivamente&#46; La IL-8 fue mayor en G1 &#40;18&#44;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>44&#44;64 versus 4&#44;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;23<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;033&#41;&#46; Los niveles de IL-8 se correlacionaron con TNF&#945; &#40;0&#44;942&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">&#8722;3</span>&#41;&#44; IL-6 &#40;0&#44;490&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;011&#41; y escala visual anal&#243;gica<span class="elsevierStyleInf">dolor radicular</span> &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;297&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;047&#41;&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">IL-17 fue mayor en pacientes con movilidad restringida de la columna lumbar &#40;9&#44;64<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#44;77 versus 1&#44;19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;54<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;014&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Nuestros resultados proporcionan evidencia de que la IL-8 y el TNF&#945; juegan un papel en el dolor lumbar y en el dolor radicular debido a la degeneraci&#243;n o a hernia discal&#46; Estos hallazgos podr&#237;an potencialmente ser utilizados por estudios futuros para desarrollar nuevas estrategias terap&#233;uticas no espec&#237;ficas para el dolor lumbar&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n y objetivos"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Materiales y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
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        "etiqueta" => "Fig&#46; 1"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Receiver operating characteristic curve &#40;ROC&#41; showing the discriminative value of IL-8 between LBP and pain-free controls&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Restricted&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;09<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;83<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TNF&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;11<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#46;92&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;324&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;64<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>44&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;53&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;235&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;64<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#46;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;725&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;42<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;151&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;42<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;65&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IL-17&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IL-22&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IL-23&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 21735743
Original language: English

DOI:10.1016/j.reumae.2022.07.002

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