ANTITUMOR NECROSIS FACTOR-ALPHA THERAPY SUPPRESSES THE INDUCTION OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS IN MICE BY INHIBITING ANTIGEN PRIMING

Purpose. Experimental autoimmune uveoretinitis (EAU) serves as a model for several immune-mediated diseases that affect the eye in humans. P revious studies indicated that tumor necrosis factor alpha (TNF-alpha) has an important proinflammatory role in EAU and possibly in human uv eitis. In this study, the authors investigated the effect of anti-TNF- alpha therapy on EAU in mice. Methods. Experimental autoimmune uveoret initis was induced in B10.A mice by immunization with interphotorecept or retinoid-binding protein (IRBP). The mice were treated with 100 or 300 mu l rabbit antiserum or polyclonal antibodies to human TNF-alpha. The treatment spanned either the afferent or the efferent stage of EA U (days-1, 1, 3, 5, 7, or days 8, 10, 12, 14, 16, respectively). Contr ol animals were injected with preimmune rabbit serum at the correspond ing times or were not treated. Three weeks after immunization, EAU was assessed by clinical evaluation and by histopathology. Immunologic re sponses were assessed by delayed-type hypersensitivity (DTH), lymphocy te proliferation to IRBP, and relative abundance of IRBP-primed spleno cytes. Results. The treatment with rabbit anti-TNF-alpha serum signifi cantly ameliorated disease when given during the afferent stage but ha d no effect when given during the efferent stage of EAU. The effect on DTH, lymphocyte proliferation, and abundance of antigen-reactive cell s roughly paralleled the effect on disease. Conclusions. Neutralizatio n of systemic TNF ameliorates EAU. The effectiveness of afferent treat ment in comparison to the treatment during the efferent stage, togethe r with the reduced proliferation and the reduced abundance of IRBP-res ponsive cells, suggest that interference with afferent-acting processe s such as antigen priming is important to achieve protection from EAU by anti-TNF treatment.