LEFLUNOMIDE - INHIBITION OF S-ANTIGEN INDUCED AUTOIMMUNE UVEITIS IN LEWIS RATS

Leflunomide (LEF) is a novel immunomodulator which has been reported t o be efficacious in experimental models of systemic autoimmune disease s and in treating rheumatoid arthritis in man. Leflunomide's ability t o ameliorate ocular disease processes was investigated in a model of a utoimmune eye disease, experimental autoimmune uveitis (EAU). EAU was induced by the injection of retinal S-antigen (S-Ag) into the foot-pad of Lewis rats. Leflunomide, or the reference compound cyclosporin A ( CSA), was administered orally or topically (to one eye) each day begin ning on the day of S-Ag injection. Drug efficacy was measured by the s uppression in clinical signs of ocular inflammation and confirmed by h istology. Both oral and topical ocular treatment with LEF suppressed t he ocular disease signs and symptoms and retinal necrosis and reduced the S-Ag antibody levels associated with EAU in a dose-dependent manne r. Both LEF and CSA were able to inhibit totally the disease manifesta tions of EAU; however, a comparison of the IC50 and IC90 values indica te that LEF is more potent than CSA in inhibiting EAU. These results s uggest that leflunomide may be useful for treating autoimmune diseases of the eye.