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.