Combined anti-interleukin-2 receptor and low-dose cyclosporine therapy in experimental autoimmune uveoretinitis

Abstract

The effect of combination treatment with anti-interleukin-2 (IL-2)-receptor monoclonal antibody (ART18) and cyclosporine A (CsA) on the effector stage of experimental autoimmune uveoretinitis (EAU) was examined. Efferent-stage EAU was induced in Lewis rats by adoptive transfer of a T-helper cell line specific to retinal soluble antigen (SAg). Rats were treated with ART18 (0.5 mg/kg/day), low dose CsA (1.5 mg/kg/day), or a combination of both. The results were compared to groups treated with high dose CsA (10 mg/kg/day) and to sham-treated animals, with respect to clinical and histological EAU, lymphocyte proliferative responses to SAg, and the ability to transfer EAU to secondary recipients. Ten-day combination therapy with ART18 and low-dose CsA was more effective than high-dose CsA and almost completely suppressed EAU development. ART18 as sole therapy was partially effective, and was better than low dose CsA as sole therapy. Splenocytes of protected animals did not transfer EAU to secondary recipients, while splenocytes of sham-treated controls did, suggesting that the number of uveitogenic lymphocytes in the treated host was reduced by the therapy. In contrast, this therapy was completely ineffective against EAU induced by active immunization. The possible reasons for this discrepancy between the two respective models of EAU are discussed.