Immunological effects of allopurinol in the treatment of experimental autoimmune uveitis (EAU) after onset of the disease.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Grus
F H
FH
Department of Ophthalmology, University of Mainz, Germany. f@grus.de
Augustin
A J
AJ
Loeffler
K
K
Lutz
J
J
Pfeiffer
N
N
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D019393:Arrestin; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D015153:Blotting, Western; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D007114:Immunization; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000276:immunology; D015866:Uveitis, Posterior / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology
D000276:Adjuvants, Immunologic; D019393:Arrestin; D001323:Autoantibodies; D001324:Autoantigens; D000493:Allopurinol