Characterization of T lymphocyte subtypes in endotoxin-induced uveitis and effect of pentoxifylline treatment

Abstract

Purpose. The aims of the study were twofold: 1) to investigate the role of T lymphocyte subtypes in the pathogenesis of endotoxin-induced uveitis (EIU) and 2) to study the possible beneficial effect of pentoxifylline, an inhibitor of neutrophil motility, and Tumor Necrosis Factor-a on this disease. Methods. Forty-two inbred male Lewis rats were divided into seven equal groups. 200 µg of Escherichia coli 055: B55 lipopolysaccharide (LPS) was injected in one hind footpad of the Group 2, 3, 4, 5, 6, and 7 rats. Group 5, 6, and 7 rats also received concomitant intraperitoneal pentoxifylline (PTX) during food pad injection of LPS. Group 1 rats were used as controls with intra-peritoneal normal saline injection. Eight, 24, and 48 hours after treatment, the rats were euthanized. Neutrophil leukocyte, mononuclear cells, and CD4+, CD8+, and CD45RA+ cell infiltration in the anterior uveal tissue were determined either by hematoxylin-eosin or monoclonal antibody staining. Tumor Necrosis Factor-a (TNF-a) levels were also measured in the aqueous and blood samples. We compared the numbers of infiltrating cells in the different groups. Results. We found that peak infiltration of lymphocyte, neutrophils, and CD4+ cells occurred at 24 hours. However, CD8+ and CD45RA+ cell number reached their highest levels at 48 hours. There was no inflammatory cell infiltration in the control rats. Concomitant pentoxifylline treatment did not affect any of these parameters, although it effectively reduced TNF-a concentrations in the anterior chamber and the serum. Conclusion. We conclude that, 1) T lymphocytes might be involved in the pathogenesis of endotoxin-induced uveitis. 2) The potential role of pentoxifylline in the treatment of human uveitis is questionable. However, these are initial findings and need confirmation by additional studies.