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

Objective and Design: Anti-arthritic effect of FTY720, a novel immunosuppressant, was compared with those of immunosuppressants cyclosporin A and tacrolimus 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 tacrolimus (0.3-3 mg/kg) were orally administered to rats for 21 days beginning on the day (day 0) of adjuvant inoculation. In addition, the anti-arthritic effect of FTY720 (0.3 mg/kg) and cyclosporin A (10 mg/kg) were evaluated by administration to animals for 5 consecutive days (days 2-6, 6-10, and 10-14). Methods: Adjuvant-induced arthritis was produced by intradermal injection of 0.5 mg heat-killed Mycobacterium tuberculosis. Hindpaw edema was measured plethysmographically. The day of arthritis onset was determined macroscopically. Bone degradation was determined by radiography. Peripheral blood leukocytes were classified microscopically. Results: All test compounds inhibited the incidence of arthritis, hindpaw edema and bone destruction. In addition, FTY720 but not cyclosporin A or tacrolimus markedly decreased the number of peripheral blood lymphocytes. FTY720 treatment on days 6 to 10 inhibited the bone destruction and hindpaw edema. Conclusion: These results suggest that the anti-arthritic effect of FTY720 in this adjuvant-induced arthritic model was more potent than those of cyclosporin A and tacrolimus. FTY720 administered on days 6 to 10 showed the inhibitory effect on the bone destruction and hindpaw edema. FTY720 may be effective in the treatment of rheumatoid arthritis.