Allopurinol has immunomodulating activity following topical and systemic application in experimental autoimmune uveitis

PURPOSE. Allopurinol has beneficial effects in the systemic treatment of le ns-induced uveitis and experimental autoimmune uveitis (EAU). This is belie ved to be due to a reduction of oxidative tissue damage through its dose-de pendent free radical scavenging ability, and to an immunomodulating effect. The purpose of this study was to demonstrate the immunological effects on the IgG-antibody repertoire in EAU after topical and systemic allopurinol a nd steroids. METHODS. We assigned 43 male Lewis rats to 6 different groups: healthy rats (BASE, n=3), EAU without therapy (CTRL, n=9); systemic treatment with allo purinol (ALSYS, n=9, 50 mg/kg body wt.i.v., given every three days for two weeks), topical allopurinol (ALLOC, n=6, 8 times/day), systemic methylpredn isolone (STSYS, n=10, 7.5 mg/kg body wt. i.v. (Hoechst, Frankfurt, Germany) ), and topical treatment with prednisolone acetate 1 % (Inflanefran Forte ( R)) (STLOC, n=6). Sera were tested against Western blots (WB) of SDS-PAGE ( sodium-dodecyl-sulfate polyacrylamide-gelelectorphoresis) of retinal protei ns. Based on digital image analysis, discriminance was analysed. RESULTS. The analysis of discriminance indicated that all therapy groups we re significantly different from untreated controls (Wilks' lambda=0.174; p <0.01). Comparing only the number of peaks and the intensities, the WB of a llopurinol treated animals showed a much stronger, significant, immunomodul ating effect than those treated with steroids (p >0.05), even after topical application (p <0.01). CONLCUSIONS. Allopurinol had an immunomodulating effect in EAU. Surprisingl y, the topical application had more effect than systemically applied allopu rinol. Allopurinol had stronger effects than systemic or topical steroids. Allopurinol appears to offer promise in the treatment of uveitis. Topical a pplication of the drug helps to reduce possible complications such as the a llopurinol hypersensitivity syndrome.