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Effects of Allopurinol on T-cells and Cytokine Profile in Experimental Autoimmune Uveitis (EAU)

1Repp A., 1Grus F. H., 1Hambek D., 2Augustin A. J., 1Pfeiffer N.,
1Johannes-Gutenberg-Universität Mainz, Universitäts-Augenklinik (Mainz)
2Städtisches Klinikum Karlsruhe, Augenklinik (Karlsruhe)

Purpose: Allopurinol is a well-known antioxidative and anti-inflammatory agent. Previous studies using different animal models of uveitis provide evidence that allopurinol changes the autoantibody repertoire and influences the T-cell proliferation. The purpose of this study was to assess the effect of allopurinol on the cytokine profile of T-cells in animals suffering from EAU.
Method: 11 male Lewis rats were divided into three groups. 6 animals were immunized with crude retinal extract, Freund`s Adjuvans and pertussis toxine: 3 of them were left untreated (EAU) and 3 received allopurinol treatment (50 mg/kg bw i.v.; ALLO). 5 healthy rats served as control (CONTROL). Furthermore a subset of T-cells of each group was treated in vitro with allopurinol. Intracellular staining was performed using anti-cytokine fluorochrome-conjugated antibodies (anti- interleukin 2,4,6 and interferon gamma). Flow cytometric analysis (FACScan) allowed the characterization of individual cytokine-producing T-lymphocytes.
Results: The FACScan confirmed a significant (p<0,05) reduction of cytokine production (interleukin 2,4 and 6) after systemically applied allopurinol as well as after in vitro treatment for 72 h in all groups. The analysis of INF-gamma revealed different results: application of allopurinol in vitro for 24 h resulted in a reduction of INF-gamma positive cells in the groups EAU and ALLO. However, the production of INF-gamma increased after 72 h treatment in these groups.
Conclusions: In this study allopurinol could demonstrate immunological effects in the cytokine production of T-cells. Regarding the effect of allopurinol on INF-gamma production allopurinol not only leads to a general immunsuppression, rather an immunmodulation. Along with its antioxidative effects described in previous studies, allopurinol might be of useful therapeutic value in the treatment of uveitis.
DFG (AU 126/2)