Colchicine—Update on mechanisms of action and therapeutic uses

• Published in: Seminars in arthritis and rheumatism Vol. 45; no. 3; pp. 341 - 350
• Main Authors: Leung, Ying Ying, Yao Hui, Laura Li, Kraus, Virginia B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2015
• Subjects: Arthritis, Gouty - drug therapy; Arthritis, Gouty - metabolism; Colchicine - therapeutic use; Colchicines; Gout - drug therapy; Gout - metabolism; Gout Suppressants - therapeutic use; Humans; Inflammation; Mechanism of action; Pharmacokinetics; Rheumatology; Therapeutic use; Tubulin - metabolism; Bcl-2; CRP; NO; BD; TNFα; ABCB1; ROCK; SRF; CYP3A4; MyD88; Colchicines; Therapeutic use; ASC; NF-κB; MDR1; NSAIDs; IC50; SNPs; P2X2; TLR; Mechanism of action; FMF; purinergic receptors P2X2; MICL; IL; MLCK; P-gp; CCF; Caspase; Inflammation; MSU; RhoA; Ca2; NALP3; ROS; TGF-β1; VGEF; Pharmacokinetics; ATP; CPPD; C-reactive protein; nuclear factor κB; toll-like receptors; myosin light chain kinase; Ca 2; myeloid differentiation primary response gene 88; Ras homolog gene family, member A; adenosine triphosphate-binding cassette transporter 1; Rho-associated, coiled-coil containing protein kinase; familial Mediterranean fever; transforming growth factor beta-1; single nucleotide polymorphisms; nitric oxide; cytochrome P450 3A4; crystal-derived chemotactic factor; 50% inhibitory concentration; IC 50; tumor necrosis factor α; cysteine-dependent aspartate-directed proteases; NACHT-LRRPYD-containing protein 3; reactive oxygen species; interleukin; apoptosis-associated Speck-like protein containing Caspase recruitment domain; Behcetʼs disease; B-cell lymphoma 2; calcium; myeloid inhibitory C-type lectin-like receptor; monosodium urate crystals; P2X7; non-steroidal anti-inflammatory drugs; P-glycoprotein 1; vascular endothelial growth factor; adenosine triphosphate; calcium pyrophosphate dihydrate crystals; serum response factor; multidrug resistance gene-1
• ISSN: 0049-0172; 1532-866X; 1532-866X
• DOI: 10.1016/j.semarthrit.2015.06.013

To review the literature and provide an update on the mechanisms of action and therapeutic uses of oral colchicine in arthritis and inflammatory conditions. 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. 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. Further understanding of the mechanisms of action underlying the therapeutic efficacy of colchicine will lead to its potential use in a variety of conditions.