Amelioration of type II collagen induced arthritis in rats by treatment with sodium diethyldithiocarbamate

Objective. Sodium diethyldithiocarbamate (Ditiocarb, DDTC), which is used i n the treatment of heavy metal poisoning, effectively inhibits NF-kappa B a ctivation and cytokine secretion in vitro. To investigate the antiinflammat ory and immunosuppressive potency of DDTC, we examined its influence on the course of collagen induced arthritis in rats. Methods. Arthritis was induced in female DA rats by injection of rat collag en type II emulsified in incomplete Freund's adjuvant into the tail base. A fter onset of arthritis, the animals received DDTC or vehicle by intraperit oneal injections or subcutaneous infusion using osmotic pumps. Disulfiram, which is cleaved into DDTC within the gastrointestinal tract, was administe red orally via gastric gavage. The course of arthritis was followed by clin ical scoring and measurement of joint swelling. Results. Collagen induced arthritis was significantly ameliorated by intrap eritoneal injection (2 x 300 mg/kg/day) and subcutaneous infusion (120 mg/k g/day) of DDTC and by enteral administration of disulfiram (200 and 300 mg/ kg/day). Conclusion. Dithiocarbamates may provide an effective new approach for the treatment of arthritis and other inflammatory diseases.