Suppression of murine collagen-induced arthritis by treatment with a novel thiazole derivative, SM-8849.
The antiarthritic activity of a novel thiazole derivative, SM-8849, was compared with that of indomethacin and D-penicillamine, in mice with collagen-induced arthritis. SM-8849 reduced the incidence and severity of disease in collagen-immunized mice, as assessed by clinical observation. This efficacy was also confirmed by radiographic and histologic studies. Indomethacin produced an apparent reduction of the clinical score, but had only a marginal effect on bone destruction. D-penicillamine did not produce any improvement. Unlike indomethacin and D-penicillamine, SM-8849 reduced the serum levels of anti-type II collagen antibodies. Flow cytometric analysis of spleen cells from arthritic mice revealed an increase in T cells expressing activation antigens (class II antigens) in comparison with normal mice. Treatment with SM-8849, but not indomethacin or D-penicillamine, prevented the increase in Ia-bearing T cells. The results suggest that an effect of SM-8849 on immunocompetent cells may be responsible for the antiarthritic activity of the compound, and this would distinguish its action from that of traditional antirheumatic drugs.
Nishikaku
F
F
Research Laboratories, Sumitomo Pharmaceuticals Co. Ltd., Osaka, Japan.
Koga
Y
Y
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D003094:Collagen / Q000276:immunology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007075:Immunoglobulin M / Q000097:blood; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010396:Penicillamine / Q000494:pharmacology / Q000627:therapeutic use; D011859:Radiography; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*
D001713:Biphenyl Compounds; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D013844:Thiazoles; C072865:4-(1-(2-fluoro-4-biphenyl)ethyl)-2-methylaminothiazole; D003094:Collagen; D010396:Penicillamine; D007213:Indomethacin