Interleukin-10 suppresses hepatic ischemia reperfusion injury in mice: Implications of a central role for nuclear factor kappa B

Ischemia/reperfusion injury of the liver requires the participation of proi nflammatory cytokines, chemokines, and adhesion molecules, many of which ar e regulated by the transcription factor nuclear factor kappa B (NF kappa B) , The antiinflammatory cytokine, interleukin-10 (IL-10) affects inflammator y reactions, at least in part, through inhibitory effects on the transcript ion factor, NF kappa B. The objective of the current study was to determine whether IL-10 could suppress hepatic ischemia/reperfusion-induced NF kappa B activation and the ensuing inflammatory liver injury. C57BL/6 mice under went partial hepatic ischemia and reperfusion with or without intravenous i njections of recombinant murine IL-10, Hepatic NF kappa B activation was in duced in a time-dependent fashion. IL-10 suppressed NF kappa B activation a s well as messenger RNA expression of tumor necrosis factor-alpha (TNF-alph a) and macrophage inflammatory protein-2 (MIP-2). In addition, IL-10 reduce d serum levels of TNF-alpha and MIP-2, Hepatic neutrophil recruitment, live r edema, and hepatocellular injury were all significantly reduced by IL-10, The data suggest that IL-10 protects against hepatic ischemia/reperfusion injury by suppressing NF kappa B activation and subsequent expression of pr oinflammatory mediators.