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 infi ltration of inflammatory cells into the synovium and destructive damag e of articular cartilage and bone. This study was performed to elucida te the effects of a novel thiazole derivative (SM-8849; (4[1-(2-fluoro -4-biphenylyl)-ethyl]-2-methylamino thiazole) in comparison with the c yclooxygenase inhibitor, indomethacin, on disease development and immu ne 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 thi s model. In contrast, SM-8849 was effective in arresting the progressi on 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 perit oneal cavity and spleen was reduced with SM-8849 treatment. These find ings suggest that NZB/KN mice are of use in the evaluation of intrinsi c antiarthritic activity, independently of cyclooxygenase inhibition. Additionally, the therapeutic value of SM-8849 is strongly suggested b y its efficacy in this model.