Role of inflammatory cytokines in induction of anterior chamber-associated immune deviation

Abstract

Purpose: To determine the extent to which proinflammatory cytokines [(interleukin-1-beta (IL-1ß), tumor necrosis factor-alpha (TNFa), gamma-interferon (?-IFN)] interfere with induction of anterior chamber-associated immune deviation (ACAID). Methods: Proinflammatory cytokines were injected intracamerally prior to local injection of ovalbumin (OVA), or added to cultures containing peritoneal exudate cells (PEC), transforming growth factor-beta (TGFß), and OVA. After incubation, 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 later. Results: Eyes pretreated with IL-1ß, TNFa or ?-IFN failed to support ACAID induction. In addition, IL-1ß and ?-IFN robbed OVA-pulsed, TGFß-treated PEC of their ability to induce ACAID, whether the inflammatory cytokines were added prior to, simultaneously with, or after exposure to TGFß. By contrast, in-vitro exposure of PEC to TNFa was unable to prevent TGFß-promoted ACAID. Conclusion: IL-1ß, ?-IFN, and TNFa injected intracamerally rob the eye of immune privilege and prevent ACAID induction. In the cases of IL-1ß and ?-IFN, ACAID seems to be prevented by a direct action of the cytokines on antigen-presenting cells (APCs). In the case of TNFa, prevention of ACAID in vivo probably occurs by an APC-independent mechanism.