Effect of FTY720, a novel immunosuppressant, on adjuvant-induced arthritisin rats

Objective and Design: Anti-arthritic effect of FTY720, a novel immunosuppre ssant, was compared with those of immunosuppressants cyclosporin A and tacr olimus in adjuvant- induced arthritis in rats. Material: Male LEW rats. Treatment. FTY720 (0.03-0.3 mg/kg), cyclosporin A (1-10 mg/kg) or tacrolimu s (0.3-3 mg/kg) were orally administered to rats for 21 days beginning on t he day (day 0) of adjuvant inoculation. In addition, the anti-arthritic eff ect of FTY720 (0.3 mg/kg) and cyclosporin A (10 mg/kg) were evaluated by ad ministration to animals for 5 consecutive days (days 2-6, 6-10, and 10-14). Methods: Adjuvant-induced arthritis was produced by intradermal injection o f 0.5 mg heat-killed Mycobacterium tuberculosis. Hindpaw edema was measured plethysmographically. The day of arthritis onset was determined macroscopi cally. Bone degradation was determined by radiography. Peripheral blood leu kocytes were classified microscopically. Results: All test compounds inhibited the incidence of arthritis, hindpaw e dema and bone destruction. In addition, FTY720 but not cyclosporin A or tac rolimus markedly decreased the number of peripheral blood lymphocytes. FTY7 20 treatment on days 6 to 10 inhibited the bone destruction and hindpaw ede ma. Conclusion: These results suggest that the anti-arthritic effect of FTY720 in this adjuvant-induced arthritic model was more potent than those of cycl osporin A and tacrolimus. FTY720 administered on days 6 to 10 showed the in hibitory effect on the bone destruction and hindpaw edema. FTY720 may be ef fective in the treatment of rheumatoid arthritis.