Systemic Interferon-γ Suppresses the Development of Endotoxin-Induced Uveitis in Mice

Abstract

Purpose: It has been shown that interferon (IFN)-γ is involved in the development of endotoxin-induced uveitis (EIU), but its exact role is unclear. We aimed to elucidate the role that endogenous systemic IFN-γ plays in EIU pathogenesis.Methods: EIU was induced in wild-type (WT) or IFN-γ knockout (GKO) mice on the C57BL/6 background by injecting Salmonella typhimurium endotoxin into a hind footpad. Twenty-four hours later, the eyes were harvested for histological analysis, and the serum was collected for cytokine ELISAs. WT and GKO mice were also intraperitoneally injected with 1 microg of recombinant murine IFN-γ (rmIFN-γ) just after and 6 h after EIU induction, and their eyes and sera were evaluated 24 h after EIU induction, as above.Results: The GKO mice had significantly more severe EIU as determined by the number of ocular infiltrating cells and lower serum IL-6 levels after EIU induction compared to WT mice. The injection of rmIFN-γ suppressed the severity of EIU and increased the serum IL-6 levels in both the WT and GKO mice.Conclusions: Endogenous IFN-γ suppresses EIU pathogenesis. In addition, the systemic administration of IFN-γ suppresses EIU. The suppressive mechanism involved is unclear but may relate to the production of IL-6.