Prevention of spontaneous polyarthritis in NZB/KN mice by treatment with a novel thiazole derivative, SM-8849.
NZB/KN mice spontaneously develop polyarthritis, characterized by infiltration of inflammatory cells into the synovium and destructive damage of articular cartilage and bone. This study was performed to elucidate the effects of a novel thiazole derivative (SM-8849; (4-[1-(2-fluoro-4-biphenylyl)-ethyl]-2-methylamino thiazole) in comparison with the cyclooxygenase inhibitor, indomethacin, on disease development and immune disorders in NZB/KN mice. Mice were treated with SM-8894 (50 mg/kg) or indomethacin (2 mg/kg), starting from two months of age, for seven months. Indomethacin had no inhibitory effect on joint lesions in this model. In contrast, SM-8849 was effective in arresting the progression of arthritis, as confirmed by histologic and radiographic studies. Moreover, SM-8849, but not indomethacin, suppressed rheumatoid factor production. In addition, the population of CD5+ B cells in the peritoneal cavity and spleen was reduced with SM-8849 treatment. These findings suggest that NZB/KN mice are of use in the evaluation of intrinsic antiarthritic activity, independently of cyclooxygenase inhibition. Additionally, the therapeutic value of SM-8849 is strongly suggested by its efficacy in this model.
Research Laboratories, Sumitomo Pharmaceuticals Company, Osaka, Japan.
F
F
Nishikaku
K
K
Nakamura
S
S
Kashiwazaki
Y
Y
Koga
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001168:Arthritis / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D005528:Foot / Q000000981:diagnostic imaging / Q000473:pathology; D006614:Hindlimb / Q000000981:diagnostic imaging / Q000473:pathology; D007213:Indomethacin / Q000627:therapeutic use; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010529:Peritoneal Cavity / Q000166:cytology; D011859:Radiography; D012217:Rheumatoid Factor / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013844:Thiazoles / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D013844:Thiazoles; C072865:4-(1-(2-fluoro-4-biphenyl)ethyl)-2-methylaminothiazole; D012217:Rheumatoid Factor; D007213:Indomethacin