Effects of immunomodulation with interferon-γ on hepatic ischemia-reperfusion injury

The development of an inflammatory response after injury depends on the participation of a variety of cell populations and endogenous mediators. Interferon-γ (IFN-γ) is a potent cellular immunomodulating cytokine that contributes to acute and chronic inflammation. In this study, the effects of immunomodulation on ischemia-reperfusion injury were examined using increasing doses of recombinant, rabbit-specific IFN-γ in an in situ model of hepatic ischemia-reperfusion. Pretreatment with low dose IFN-γ augmented injury as measured by histology, aminotransferase concentrations, and myeloperoxidase activity. By contrast, high dose IFN-γ pretreatment, equivalent to IFN-γ supplements used in clinical trials, resulted in a lack of neutrophil infiltration and minimal progression of late phase, neutrophil-mediated reperfusion injury. These results suggest that immunomodulating mediators such as IFN-γ may play a regulating role in the evolution of ischemia-reperfusion, contributing to the development and resolution of acute hepatic injury.