Effect of a novel anti-rheumatic 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 type 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 production of IL-6 by murine synovial fibroblasts stimulated with recombinant interleukin 1 (IL-1) beta in a dose-dependent manner (0.1-10 microM). Neither the general protein synthesis nor the expression of type I IL-1 receptor was affected by TA-383. The results show that TA-383 possesses an inhibitory activity on IL-6 generation and suggest that the effect may partly contribute to the anti-arthritic effect of TA-383.
Sugita
T
T
Research Laboratory of Applied Biochemistry, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Ueno
M
M
Furukawa
O
O
Murakami
T
T
Takata
I
I
Tosa
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001168:Arthritis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D003094:Collagen / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013583:Synovial Membrane / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D015850:Interleukin-6; C083037:2-(4-chlorophenyl)-4,5-diphenyl-2-imidazoline hydrochloride; D003094:Collagen