Amelioration of type II collagen induced arthritis in rats by treatment with sodium diethyldithiocarbamate.
OBJECTIVE
Sodium diethyldithiocarbamate (Ditiocarb, DDTC), which is used in the treatment of heavy metal poisoning, effectively inhibits NF-kappaB activation and cytokine secretion in vitro. To investigate the antiinflammatory 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 collagen type II emulsified in incomplete Freund's adjuvant into the tail base. After onset of arthritis, the animals received DDTC or vehicle by intraperitoneal injections or subcutaneous infusion using osmotic pumps. Disulfiram, which is cleaved into DDTC within the gastrointestinal tract, was administered orally via gastric gavage. The course of arthritis was followed by clinical scoring and measurement of joint swelling.


RESULTS
Collagen induced arthritis was significantly ameliorated by intraperitoneal injection (2 x 300 mg/kg/day) and subcutaneous infusion (120 mg/kg/day) of DDTC and by enteral administration of disulfiram (200 and 300 mg/kg/day).


CONCLUSIONS
Dithiocarbamates may provide an effective new approach for the treatment of arthritis and other inflammatory diseases.
Voll
R E
RE
Department of Internal Medicine III, University of Erlangen-Nürnberg, Erlangen, Germany.
Mikulowska
A
A
Kalden
J R
JR
Holmdahl
R
R
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003094:Collagen / Q000276:immunology; D004195:Disease Models, Animal; D004221:Disulfiram / Q000008:administration & dosage; D004050:Ditiocarb / Q000008:administration & dosage* / Q000009:adverse effects; D004333:Drug Administration Routes; D005260:Female; D015918:Infusion Pumps, Implantable; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011355:Prodrugs / Q000008:administration & dosage; D051381:Rats; D012720:Severity of Illness Index; D013643:Tarsus, Animal / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D016328:NF-kappa B; D011355:Prodrugs; D003094:Collagen; D004050:Ditiocarb; D004221:Disulfiram