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Colchicine: Its mechanism of action and efficacy in crystal-induced inflammation

  • George Nuki
Article

Abstract

New light has been shed on the mechanisms of action of colchicine in crystal-associated arthropathies. Colchicine, long used to treat gout, arrests microtubule assembly and inhibits many cellular functions. At micromolar concentrations, it suppresses monosodium urate crystal-induced NACHT-LRR-PYD-containing protein-3 (NALP3) inflammasome-driven caspase-1 activation, IL-1β processing and release, and L-selectin expression on neutrophils. At nanomolar concentrations, colchicine blocks the release of a crystal-derived chemotactic factor from neutrophil lysosomes, blocks neutrophil adhesion to endothelium by modulating the distribution of adhesion molecules on the endothelial cells, and inhibits monosodium urate crystal-induced production of superoxide anions from neutrophils. Cytochrome P450 3A4, the multidrug transporter P-glycoprotein, and the drugs that bind these proteins influence its pharmacokinetics and pharmacodynamics. Trial evidence supports its efficacy in acute gout and in preventing gout flares, but it has narrow therapeutic index, and overdosage is associated with gastrointestinal, hepatic, renal, neuromuscular, and cerebral toxicity; bone marrow damage; and high mortality.

Keywords

Colchicine Gout Gouty Arthritis CPPD Acute Gout 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Osteoarticular Research Group, The Queen’s Medical Research InstituteUniversity of EdinburghEdinburghScotland, UK

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