Immunomodulating activity of allopurinol in experimental lens-induced uveitis.
OBJECTIVE
The aim of this study was to evaluate the immunomodulating activity of allopurinol using a model of lens-induced uveitis (LIU) and to compare these effects to those of steroids.


METHODS
We tested the sera of both LIU and control rats against western blots (WB) of SDS-PAGE separations of protein fractions from normal and LIU rat lenses. These blots were scanned using digital image analysis. A newly developed technique was used to compare the complex autoantibody (AAB) repertoires. Five groups of LIU rats were investigated: no treatment; single doses of methylprednisolone (MPR; 7.5 mg/kg body wt.i.v.); allopurinol (AL; 50 mg/kg body wt. i.v.); a combination of both drugs (AL and MPR); repeated application of AL (ALFR; 50 mg/kg body wt.i.v. every 2 weeks during the immunization period and a daily dose of approx. 25 mg/kg body wt. orally).


RESULTS
Immunization induced complex antibody repertoires against lens proteins. Antibody repertoires of LIU rats were identical, regardless of whether the proteins were obtained from control, uveitis eyes, or corresponding healthy eyes of the same individual. AL showed a dose-dependent immunological effect in LIU treatment. Given as a single dose, AL revealed no significant change in the AAB repertoire; however, ALFR showed very clear modification of the AAB repertoires compared to both controls and rats receiving steroids.


CONCLUSIONS
These results suggest dose-dependent effects of allopurinol in LIU treatment. Repeated application during the immunization period induced a strong immunomodulating effect of AL that was not observed after single doses.
Grus
F H
FH
Department of Ophthalmology, University of Bonn, Germany.
Augustin
A J
AJ
Zimmermann
C W
CW
Spitznas
M
M
Sekundo
W
W
Lutz
J
J
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000493:Allopurinol / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000494:pharmacology*; D001323:Autoantibodies / Q000032:analysis / Q000187:drug effects; D001324:Autoantigens; D015153:Blotting, Western; D003459:Crystallins; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D004591:Electrophoresis, Polyacrylamide Gel; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy*
D000276:Adjuvants, Immunologic; D000963:Antimetabolites; D001323:Autoantibodies; D001324:Autoantigens; D003459:Crystallins; D005938:Glucocorticoids; D000493:Allopurinol; D008775:Methylprednisolone