TACROLIMUS-RAPAMYCIN COMBINATION THERAPY FOR EXPERIMENTAL AUTOIMMUNE UVEORETINITIS

Tacrolimus and rapamycin both belong to a new family of immunosuppress ants, immunophilin ligands, but the mechanisms by which they inhibit T cell activation are different. Therefore, we tested the immunosuppres sive effects of combination therapy with low doses of tacrolimus and r apamycin on experimental autoimmune uveoretinitis (EAU) in rats. Male Lewis rats, immunized with S-antigen (S-Ag) were given intraperitoneal injection of the combined drugs for 14 days after the immunization wi th S-Ag. Effects were evaluated by clinical observations, histological examination and immune response. The combination therapy with tacroli mus (0.1 mg/kg per day) and rapamycin (0.03 mg/kg per day) achieved 10 0% suppression of clinical EAU and 66.7% suppression of histological E AU; tacrolimus combined with a higher dose of rapamycin (0.1 mg/kg per day) caused 100% suppression clinically and histologically. Therapy w ith either drug alone achieved only partial suppression: tacrolimus al one (0.1 or 0.2 mg/kg per day) or rapamycin alone (0.03-0.2 mg/kg per day). Doubling the dose of either drug produced only 16.7% suppression with rapamycin or 50% suppression with tacrolimus. The serum antibody levels to S-Ag and proliferative response of lymphocytes to S-Ag were also significantly suppressed by the combination therapy with low dos es of tacrolimus and rapamycin. (C) 1997 Japanese Ophthalmological Soc iety.