PROTECTIVE EFFECTS OF D-PENICILLAMINE AND A THIAZOLE DERIVATIVE, SM-8849, ON PRISTANE-INDUCED ARTHRITIS IN MICE

To evaluate the antiarthritic properties of a novel thiazole derivativ e, the drugs SM-8849, D-penicillamine and indomethacin were administer ed to pristane-injected DBA/1 mice. The mice were treated daily with t he agents for 32 weeks, starting from the day of the pristane injectio n. Treatment with SM-8849 (50 mg/kg) resulted in an amelioration of ar thritic disease, as assessed by clinical, radiographic, and histologic examinations. Similar results were obtained in mice treated with 50 m g/kg D-penicillamine, although this disease modifying antirheumatic dr ug was slightly less effective than the same dose of SM-8849. In contr ast, indomethacin at the maximum tolerated dose of 2 mg/kg did not alt er the course of the disease. SM-8849 and D-penicillamine were also sh own to reduce serum levels of rheumatoid factors and the acute-phase r eactant, serum amyloid P component. Indomethacin failed to affect eith er parameter. Flow cytometric analysis revealed an elevation in the T- cell population that expressed CD44, a marker of murine memory T-cells , in spleens from pristane-injected mice. SM-8849, but not D-penicilla mine, prevented the increase in this cell population. These results le d us to conclude that pristine-induced arthritis was a useful model fo r the evaluation of antirheumatic agents, in that using this model, we were able to distinguish disease modifying antirheumatic drugs from n onsteroidal anti-inflammatory drugs. Our findings also indicate that S M-8849 shows antiarthritic activity, with a unique mechanism of action , differing from that of D-penicillamine.