Colchicine suppresses neutrophil superoxide production in a murine model of gouty arthritis: a rationale for use of low-dose colchicine.
OBJECTIVE
When used to treat gouty arthritis, colchicine is believed to work by inhibiting microtubule-dependent cell infiltration. However, in vitro, colchicine also reduces monosodium urate (MSU)-induced superoxide production by neutrophils. Our study aimed to compare the effects of colchicine on neutrophil superoxide production and infiltration in an in vivo model of acute gouty inflammation.


METHODS
In vitro: Human and murine peritoneal neutrophils were incubated with MSU with and without colchicine, and superoxide production was measured. In vivo: Mice were treated with colchicine followed by an intraperitoneal injection of MSU to induce acute inflammation. After 4h, the peritoneal cells were recovered to measure superoxide production and neutrophil infiltration. Sera were tested for liver and renal toxicity.


RESULTS
Colchicine dose-dependently inhibited MSU-induced superoxide production by both human and murine neutrophils in vitro. Oral colchicine inhibited MSU-induced superoxide production by neutrophils in vivo at doses 100 times lower than those required to inhibit neutrophil infiltration and without acute liver or renal toxicity. Neutrophils treated with colchicine in vivo still produced superoxide in response to another stimulus, 4-beta-phorbol-12-myristate-13-acetate.


CONCLUSIONS
These results show a beneficial effect of colchicine for the treatment of MSU-induced superoxide production in vivo at sub-toxic doses without compromising superoxide production by other physiological processes. This is the first in vivo data to provide a biological rationale that supports the implementation of low dose, non-toxic, colchicine therapy for the treatment of gouty arthritis.
Chia
E W
EW
Malaghan Institute of Medical Research, Wellington, New Zealand.
Grainger
R
R
Harper
J L
JL
D000208:Acute Disease; D000284:Administration, Oral; D000818:Animals; D015210:Arthritis, Gouty / Q000188:drug therapy* / Q000503:physiopathology; D003078:Colchicine / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006074:Gout Suppressants / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D006074:Gout Suppressants; D013481:Superoxides; D003078:Colchicine