Roles of Interferon (IFN)– for the Development of Endotoxin–Induced Uveitis in Mice

Abstract

Abstract: : Purpose: Although involvement of interferon (IFN)–γ in the development of endotoxin–induced uveitis (EIU) has been demonstrated, details remain to be unsolved. The aim of this study is to elucidate the role that endogenous systemic IFN–γ plays in EIU pathogenesis. Methods: EIU was induced by injection of Salmonella typhimurium endotoxin into a hind footpad, either in wild type (WT) or IFN–γ knockout (GKO) mice of the C57BL/6 background. Twenty–four hours later, the eyes were harvested for histological analysis and the serum was collected for cytokine ELISA. Both WT and GKO mice were also intraperitoneally injected with 1 µg of recombinant murine IFN–γ (rm IFN–γ) just after and 6 hours after EIU induction and their eyes and sera were similarly evaluated 24 hours after EIU induction. Results: Significantly more severe EIU as determined by the number of ocular infiltrating cells was induced in GKO mice. Serum IL–6 levels after EIU induction was significantly lower in GKO mice. The injection of rm IFN–γ suppressed the severity of EIU and increased the serum IL–6 levels in both the WT and GKO mice. Conclusions: It was clearly demonstrated that endogenous IFN–γ suppresses EIU. Additionally, exogenous IFN–γ also suppresses EIU. The suppressive mechanism involved is unclear but may relate to the serum levels of IL–6.

Keywords: uveitis-clinical/animal model • cytokines/chemokines • inflammation