Allopurinol has Immunomodulating Activity following Topical and Systemic Application in Experimental Autoimmune Uveitis

Abstract

Purpose Allopurinol has beneficial effects in the systemic treatment of lens-induced uveitis and experimental autoimmune uveitis (EAU). This is believed to be due to a reduction of oxidative tissue damage through its dose-dependent 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 and 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 allopurinol (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 methylprednisolone (STSYS, n=10, 7.5 mg/kg body wt. i.v. (Hoechst, Frankfurt, Germany)), and topical treatment with prednisolone acetate 1% (Inflanefran Forte®) (STLOC, n=6). Sera were tested against Western blots (WB) of SDS-PAGE (sodium-dodecyl-sulfate polyacrylamide-gelelectorphoresis) of retinal proteins. Based on digital image analysis, discriminance was analysed. Results The analysis of discriminance indicated that all therapy groups were significantly different from untreated controls (Wilks' lambda = 0.174; p<0.01). Comparing only the number of peaks and the intensities, the WB of allopurinol treated animals showed a much stronger, significant, immunomodulating effect than those treated with steroids (p>0.05), even after topical application (p<0.01). Conlcusions Allopurinol had an immunomodulating effect in EAU. Surprisingly, the topical application had more effect than systemically applied allopurinol. Allopurinol had stronger effects than systemic or topical steroids. Allopurinol appears to offer promise in the treatment of uveitis. Topical application of the drug helps to reduce possible complications such as the allopurinol hypersensitivity syndrome.