EFFECT OF A NOVEL ANTIRHEUMATIC DRUG, TA-383, ON TYPE-II COLLAGEN-INDUCED ARTHRITIS - SUPPRESSIVE EFFECT OF TA-383 ON INTERLEUKIN-6 PRODUCTION

We have evaluated the effect of a novel anti-rheumatic drug, cis-2-(4- chlorophenyl)-4, 5-diphenyl-2-imidazoline hydrochloride (TA-383), on t ype II collagen (CII)-induced arthritis in DBA/1J mice. Treatment with TA-383 (0.4 mg/kg/day) from the day of immunization with CII strongly suppressed the arthritic responses. Increased serum interleukin 6 (IL -6) level was lowered in parallel with the effect. Effect of TA-383 on IL-6 production was examined in vitro. TA-383 inhibited the productio n of IL-6 by murine synovial fibroblasts stimulated with recombinant i nterleukin 1 (IL-1) beta in a dose-dependent manner (0.1 - 10 muM). Ne ither the general protein synthesis nor the expression of type I IL-1 receptor was affected by TA-383. The results show that TA-383 possesse s an inhibitory activity on IL-6 generation and suggest that the effec t may partly contribute to the anti-arthritic effect of TA-383.