Immunological effect of systemically administered allopurinol in experimental autoimmune uveitis

Abstract

Allopurinol shows beneficial effects in the systemic treatment of lens-induced uveitis. This is believed to be due to the reduction of oxidative tissue damage via a dose-dependent free radical scavenging ability and an immunomodulating effect. The purpose of this study was to investigate the immunological effects in experimental autoimmune uveitis after systemic treatment with allopurinol (AL) and steroids (STER). 31 male Lewis rats were immunized with crude retinal extract, Freund's Adjuvans and pertussis toxin. The rats were divided into four groups: healthy rats (BASIS, n = 3), experimental autoimmune-uveitis without therapy (EAU, n = 9), 50 mg/kg bw. allopurinol i.v. (ALSYS, n = 9), and 7.5 mg/kg bw. methylprednisolone i.v. (STSYS, n = 10). ALSYS and STSYS received five intravenous injections during the 2 weeks immunization period. The rats' sera were tested against Western Blots (WB) of electrophoretic separations of retinal proteins. Based on digital image analysis, an analysis of discriminance was performed. The multivariate analysis of discriminance revealed a significance difference between the WBs of ALSYS and STSYS (p < 0.01) compared to EAU without therapy. The number and intensity of peaks in WBs were strongly reduced in the ALSYS group compared to EAU. AL revealed a strong immunomodulating effect in the treatment of experimental autoimmune uveitis that is markedly stronger than that of steroids. Together with the antioxidative effect of allopurinol known from previous studies, this drug could be a new promising therapeutic approach in the treatment of uveitis.