The immune response and the eye: A role for TNFα in anterior chamber- associated immune deviation

Purpose. Interleukin-1 and tumor necrosis factor (TNF) α are proinflammatory cytokines and crucial mediators in many aspects of immunity. In this study, their role in anterior chamber-associated immune deviation (ACAID) was investigated. Methods. The role of these cytokines was examined by the use of neutralizing antibodies to TNF and interleukin (IL)-1α, IL- 1β, and IL-1 receptor. These reagents were co-injected with antigen into the anterior chamber and the effect on ACAID assessed. 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 TNFα mRNA induced. Results. Neutralizing antibody to TNF, when injected with TNP-spleen cells into the anterior chamber, blocked ACAID to the TNP hapten. Antibodies to IL-1α, IL-1β, and IL-1 receptors either alone or in combination did not block the establishment of ACAID. Studies with reverse transcriptase polymerase chain reaction (Rt-PCR) confirmed that early (within 2 hours) after anterior chamber injection of TNP-cells, messenger RNA levels for TNFα were dramatically increased. The induction of ACAID to bovine serum albumin also required the production of TNFα. Further studies showed that the production of blood borne 'ACAID-inducing' signals after anterior chamber injection of bovine serum albumin or TNP-spleen were dependent on TNF. Conclusions. TNFα plays a crucial role in ACAID. Induction of TNFα within the eye may be an important event in the complex series of events that induce ACAID and possibly maintain immunologic privilege.