THE IMMUNE-RESPONSE AND THE EYE - A ROLE FOR TNF-ALPHA IN ANTERIOR CHAMBER-ASSOCIATED IMMUNE DEVIATION

Purpose. Interleukin-1 and tumor necrosis factor (TNF) a are proinflam matory cytokines and crucial mediators in many aspects of immunity. In this study, their role in anterior chamber-associated immune deviatio n (ACAID) was investigated. Methods. The role of these cytokines was e xamined by the use of neutralizing antibodies to TNF and interleukin ( IL)-1 alpha, IL-1 beta, and IL-1 receptor. These reagents were co-inje cted with antigen into the anterior chamber and the effect on ACAID as sessed. In addition, reverse transcriptase polymerase chain reaction ( RT-PCR) was performed on eyes injected with TNP-spleen or bovine serum albumin to determine the levels of TNF alpha mRNA induced. Results. N eutralizing antibody to TNF, when injected with TNP-spleen cells into the anterior chamber, blocked ACAID to the TNP hapten. Antibodies to I L-1 alpha, IL-1 beta, and IL-1 receptors either alone or in combinatio n did not block the establishment of ACAID. Studies with reverse trans criptase polymerase chain reaction (Rt-PCR) confirmed that early (with in 2 hours) after anterior chamber injection of TNP-cells, messenger R NA levels for TNF alpha were dramatically increased. The induction of ACAID to bovine serum albumin also required the production of TNF alph a. Further studies showed that the production of blood borne ''ACAID-i nducing'' signals after anterior chamber injection of bovine serum alb umin or TNP-spleen were dependent on TNF. Conclusions. TNF alpha plays a crucial role in ACAID. Induction of TNF alpha within the eye may be an important event in the complex series of events that induce ACAID and possibly maintain immunologic privilege.