allopurinol and Uveitis--Posterior

Allopurinol reduces oxidative tissue damage and exerts immunomodulating effects in the treatment of experimental autoimmune uveitis (EAU). However, the mechanism of the immunologic pathway remains unclear. In previous studies, treatment was started at the time of immunization. Therefore, whether allopurinol prevents the onset of the disease (i.e., acts in a protective manner) is not known.. Sixteen male Lewis rats were used: 6 EAU without therapy [control]; 4 EAU with allopurinol treatment starting 7 days after immunization [AL7]; and 6 EAU with allopurinol treatment starting 11 days after immunization [AL11]. Their sera were tested against Western blots of sodium dodecyl sulfate-polyacrylamide gel electrophoresis of retinal proteins. Based on digital image analysis, analysis of discriminance was done.. There were significant immunomodulating effects in both therapy groups (Wilks' lambda 0.001, P < 0.008) compared to controls. However, the effects were more pronounced in the AL7 group, where peak intensities and the number of peaks were markedly more reduced.. Immunomodulating effects of allopurinol can be detected even if the therapy starts after the onset of the disease. Thus allopurinol strongly influences the immunologic mechanism in this model of autoimmune disease. In view of its minimal side effects, the drug could be a promising alternative for the therapy and prophylaxis of uveitis and other autoimmune diseases.

Topics: Adjuvants, Immunologic; Allopurinol; Animals; Arrestin; Autoantibodies; Autoantigens; Autoimmune Diseases; Blotting, Western; Disease Models, Animal; Electrophoresis, Polyacrylamide Gel; Immunization; Male; Rats; Rats, Inbred Lew; Retina; Uveitis, Posterior

To compare the effects of allopurinol to those of prednisolone on the oxidative tissue damage and inflammatory response in experimental autoimmune uveitis (EAU).. Experiments were performed using 27 male Lewis rats. EAU was induced by means of crude retina extract, Freund's adjuvant and pertussis toxin. One group of animals served as controls and two groups were treated systemically, one with allopurinol and one with prednisolone. At the end of the experiments lipid peroxides (LPO), myeloperoxidase activity (MPO), and histological changes were determined in the retinal tissue. LPO were measured by two different methods [thiobarbituric acid reactive substances (TBARS) and malondialdehyde-like substances].. Allopurinol led to a significant reduction in LPO and MPO levels. The steroid treatment also resulted in a significant reduction in MPO activity but LPO were significantly reduced only when measured as TBARS. Histological changes were significantly reduced by allopurinol only.. Allopurinol is more effective than prednisolone in treating EAU. Its efficacy can be explained by the antioxidative/antiinflammatory and probably immunological action. The antiinflammatory effects of prednisolone are not sufficient to reduce the tissue damage. Allopurinol promises to be a useful alternative to steroids in the treatment of uveitis.

Topics: Allopurinol; Animals; Anti-Inflammatory Agents; Autoimmune Diseases; Cattle; Free Radical Scavengers; Injections, Intravenous; Lipid Peroxides; Male; Peroxidase; Prednisolone; Rats; Rats, Inbred Lew; Retina; Uveitis, Posterior