The role of tumor necrosis factor-alpha in the induction of experimental autoimmune uveoretinitis in mice.

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Abstract

PURPOSE: To examine the role of tumor necrosis factor-alpha (TNF) in the induction of experimental autoimmune uveoretinitis (EAU), the authors compared in vivo TNF production in EAU-susceptible and EAU-resistant strains of congenic mice and attempted to determine whether TNF can enhance the inflammation in EAU by injection of TNF at the time of immunization. METHODS: The production of TNF after stimulation with lipopolysaccharide (LPS) in B10.A and B10.D2 mice was measured by bioassay with L929 cells. The incidence and severity of EAU was compared between the group immunized with conventional methods and the group that alternatively received additional subcutaneous injection of recombinant human TNF (rhTNF) at the time of immunization in both B10.A and B10.D2 mice. RESULTS: Serum concentration of TNF after stimulation with 50 micrograms of LPS was significantly higher in B10.A mice than in B10.D2 mice. The incidence of EAU in B10.A mice was 60%, but it was only 10% in B10.D2 mice using the conventional method. Extremely severe chorioretinitis and iridocyclitis occurred in B10.A mice with the injection of rhTNF at the time of immunization for EAU. The incidence of EAU in B10.A and B10.D2 rose to 100% and 40%, respectively. When administered alone, rhTNF did not cause any inflammatory change in the uvea. CONCLUSIONS: The rhTNF was found to enhance the immune response to interphotoreceptor retinoid-binding protein in mice. These results suggest that susceptibility to EAU is in some part mediated by the ability of mice to produce TNF.