Colchicine—Update on mechanisms of action and therapeutic uses

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Objectives

To review the literature and provide an update on the mechanisms of action and therapeutic uses of oral colchicine in arthritis and inflammatory conditions.

Methods

We performed PubMed database searches through June 2014 for relevant studies in the English literature published since the last update of colchicine in 2008. Searches encompassed colchicine mechanisms of action and clinical applications in medical conditions. A total of 381 articles were reviewed.

Results

The primary mechanism of action of colchicine is tubulin disruption. This leads to subsequent down regulation of multiple inflammatory pathways and modulation of innate immunity. Newly described mechanisms include various inhibitory effects on macrophages including the inhibition of the NACHT-LRRPYD-containing protein 3 (NALP3) inflammasome, inhibition of pore formation activated by purinergic receptors P2X7 and P2X2, and stimulation of dendritic cell maturation and antigen presentation. Colchicine also has anti-fibrotic activities and various effects on endothelial function. The therapeutic use of colchicine has extended beyond gouty arthritis and familial Mediterranean fever, to osteoarthritis, pericarditis, and atherosclerosis.

Conclusion

Further understanding of the mechanisms of action underlying the therapeutic efficacy of colchicine will lead to its potential use in a variety of conditions.

Introduction

Colchicine is an alkaloid extracted from plants of the genus Colchicum (autumn crocus). The therapeutic use of colchicine has been well documented in gout and familial Mediterranean fever (FMF); it has also been used in other diseases including Behcetʼs disease (BD), pericarditis, coronary artery disease, and other inflammatory and fibrotic conditions. The pharmacotherapeutic mechanism of action of colchicine in diverse disorders is not fully understood. The aim of this article is to review the literature and provide an update on the mechanisms of action and therapeutic uses of colchicine in various inflammatory conditions.

Section snippets

Methods

We performed a PubMed database search for relevant studies published using the search terms “mechanism of action” OR “inflammation” OR “pharmacokinetics” OR “toxicity” OR “therapeutic use” AND “colchicine” between January 1, 2008 to June 15, 2014 and restricted to the English language. The start date was chosen to cover literature published since the topic was last comprehensively reviewed in 2008 [1], [2]. We focused on original articles that provided new information on the mechanisms of

Tubulin disruption and anti-mitotic effect of colchicine

The most studied therapeutic mechanism of action of colchicine is its capacity to bind to tubulins, thereby blocking the assembly and polymerization of microtubules. Microtubules, key components of the cytoskeleton, are made up of αβ-tubulin heterodimers. Microtubules are involved in various cellular processes including maintenance of cell shape, intracellular trafficking, cytokine and chemokine secretion, cell migration, and regulation of ion channels and cell division. Colchicine is a

Conclusion

Colchicine has been the first-line therapy for the treatment of acute gouty arthritis and FMF. Due to the anti-inflammatory and anti-fibrotic activities, the therapeutic use of colchicine has extended beyond arthritis. The exact mechanisms of action underlying its efficacy are not completely understood and remain under active investigation. Current results suggest that colchicine downregulates multiple inflammatory pathways and modulates innate immunity. As demonstrated by this review, there

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    Author contributions: All authors contributed equally and approved the final version of the manuscript.

    Funding source: This review is funded in part by the Singapore National Medical Research Council, transitional award no. (NMRC-TA-0007-2012), the National Institutes of Health, USA (NIH, P30-AG-028716) and a grant from the Duke-NUS Governing Board (Duke/Duke-NUS/RECA/2012/0005) for funding support to V.B.K. and Y.-Y.L.

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