F. Nishikaku et al., PREVENTION OF SPONTANEOUS POLYARTHRITIS IN NZB KN MICE BY TREATMENT WITH A NOVEL THIAZOLE DERIVATIVE, SM-8849/, Drugs under experimental and clinical research, 20(3), 1994, pp. 85-92
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.