ROLE OF INFLAMMATORY CYTOKINES IN INDUCTION OF ANTERIOR CHAMBER-ASSOCIATED IMMUNE DEVIATION

Purpose: To determine the extent to which proinflammatory cytokines [( interleukin-I-beta (IL-I beta), tumor necrosis factor-alpha (TNF alpha ), gamma-interferon (gamma-IFN)] interfere with induction of anterior chamber-associated immune deviation (ACAID). Methods: Proinflammatory cytokines were injected intracamerally prior to local injection of ova lbumin (OVA), or added to cultures containing peritoneal exudate cells (PEC), transforming growth factor-beta (TGF beta), and OVA. After inc ubation, these cells were washed and injected intravenously into naive , syngeneic mice. One week later, the mice were immunized with OVA in adjuvant, and delayed hypersensitivity (DH) was assessed seven days la ter. Results: Eyes pretreated with IL-I beta, TNF alpha or gamma-IFN f ailed to support ACAID induction, In addition, IL-I beta and gamma-IFN robbed OVA-pulsed, TGF beta-treated PEC of their ability to induce AC AID, whether the inflammatory cytokines were added prior to, simultane ously with, or after exposure to TGF beta. By contrast, in-vitro expos ure of PEC to TNF alpha was unable to prevent TGF beta-promoted ACAID, Conclusion: IL-I beta, gamma-IFN, and TNF alpha injected intracameral ly rob the eye of immune privilege and prevent ACAID induction. In the cases of IL-I beta and gamma-IFN, ACAID seems to be prevented by a di rect action of the cytokines on antigen-presenting cells (APCs), In th e case of TNF alpha, prevention of ACAID in vivo probably occurs by an APC-independent mechanism.