Abstract:
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 ef-fect 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.¶
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Received 21 June 1999; returned for revision 26 August 1999; returned for final revision 25 February 2000; accepted by M. Katori 9 April 2000
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Matsuura, M., Imayoshi, T., Chiba, K. et al. Effect of FTY720, a novel immunosuppressant, on adjuvant-induced arthritis in rats. Inflamm. res. 49, 404–410 (2000). https://doi.org/10.1007/s000110050608
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DOI: https://doi.org/10.1007/s000110050608