Mechanism of action of colchicine

Abstract

Colchicine suppressed the development of urate crystal-induced canine synovitis only at a dose (0.25 mg/kg) that produced a peripheral leukopenia; half that amount produced neither leukopenia nor inhibition of the inflammatory response. Colchicine in the lower dose range still had no antiinflammatory effect when the time of pretreatment was increased from 15 min to 5 h before the inflammatory challenge, and when an additional dose was given 24 h beforehand. Lower doses of Colchicine were not antiinflammatory when the drug was introduced directly into the joint, either along with the urate crystals or when the inflammatory response was present and increasing. Lumicolchicine (0.25 mg/kg) neither suppressed inflammation nor induced leukopenia. The canine model differs from human gouty inflammation and from urate crystal-induced human inflammation, both of which processes respond to small, nonleukopenic doses of colchicine.