THE EFFICACY OF LEFLUNOMIDE IN S-ANTIGEN-INDUCED AUTOIMMUNE UVEITIS

Leflunomide (LEF), an isoxazole derivative under development for the t reatment of rheumatoid arthritis, is a novel immunomodulator which has been reported to be efficacious in experimental models of transplanta tion and systemic autoimmune diseases. The ability of leflunomide to e ffect autoimmune eye disease was investigated in a model of ocular aut oimmunity, experimental S-antigen (S-Ag)-induced autoimmune uveitis (E AU). Leflunomide or the reference compound, Cyclosporin A (CSA), were administered topically to one eye or orally each day beginning on the day of S-Ag injection. Drug efficacy was measured by the suppression o f ocular inflammation. Both oral and topical treatment with LEF suppre ssed the ocular disease symptoms, retinal necrosis, and S-Ag antibody levels associated with EAU. LEF and CSA were both able to completely i nhibit EAU disease onset. A comparison of the IC50 and IC90 values sug gest that LEF is more potent than CSA in inhibiting EAU. These results indicate that leflunomide may be useful in treating ocular autoimmune diseases.