Interleukin-10 suppresses hepatic ischemia/reperfusion injury in mice: implications of a central role for nuclear factor kappaB

Hepatology. 1999 Jul;30(1):203-8. doi: 10.1002/hep.510300120.


Ischemia/reperfusion injury of the liver requires the participation of proinflammatory cytokines, chemokines, and adhesion molecules, many of which are regulated by the transcription factor nuclear factor kappaB (NFkappaB). The anti-inflammatory cytokine, interleukin-10 (IL-10) affects inflammatory reactions, at least in part, through inhibitory effects on the transcription factor, NFkappaB. The objective of the current study was to determine whether IL-10 could suppress hepatic ischemia/reperfusion-induced NFkappaB activation and the ensuing inflammatory liver injury. C57BL/6 mice underwent partial hepatic ischemia and reperfusion with or without intravenous injections of recombinant murine IL-10. Hepatic NFkappaB activation was induced in a time-dependent fashion. IL-10 suppressed NFkappaB activation as well as messenger RNA expression of tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2). In addition, IL-10 reduced serum levels of TNF-alpha and MIP-2. Hepatic neutrophil recruitment, liver 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 NFkappaB activation and subsequent expression of proinflammatory mediators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CXCL2
  • Chemotactic Factors / genetics
  • Edema
  • Inflammation
  • Intercellular Adhesion Molecule-1 / genetics
  • Interleukin-10 / pharmacology*
  • Kinetics
  • Liver / blood supply*
  • Liver / metabolism*
  • Liver / pathology
  • Liver Circulation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monokines / genetics
  • NF-kappa B / metabolism*
  • RNA, Messenger / genetics
  • Reperfusion Injury / prevention & control*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription, Genetic / drug effects
  • Tumor Necrosis Factor-alpha / genetics


  • Chemokine CXCL2
  • Chemotactic Factors
  • Monokines
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Interleukin-10