Purpose: We assessed the suppressive effect of a combination of cyclosporin (an immunosuppressive agent) and allopurinol (a xanthine oxidase inhibitor and radical scavenger) on experimental autoimmune uveoretinitis (EAU) in Lewis rats, induced by interphotoreceptor retinoid-binding protein (IRBP).
Methods: After the immunization of Lewis rats with 30 micrograms of IRBP. We administrated cyclosporin and/or allopurinol to the IRBP-immunized Lewis rats. We observed the incidence and the severity of EAU. Histological, immunological, and biochemical examinations were performal 13 days after the immunization. The suppressive effect of these drugs in vitro on the production of free radicals derived from polymorphonuclear leukocytes.
Results: The incidence of EAU was suppressed by 50% at 13 days after immunization, and in terms of clinical and histological findings, inflammatory reaction was more inhibited by the combination of these drugs than by either cyclosporin or allopurinol alone. Lymphocyte proliferation assay against IRBP was significantly inhibited by the combination of drugs. No adverse systemic effects were identified. Cyclosporin and allopurinol inhibited radical production both separately and in combination.
Conclusion: This suggests that suppression of EAU is based not only on inhibited cell-mediated immunity but also on inhibited production of free radicals derived from polymorphonuclear leukocytes.