Interleukin-10 suppresses hepatic ischemia/reperfusion injury in mice: implications of a central role for nuclear factor kappaB.
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.
Yoshidome
H
H
Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA.
Kato
A
A
Edwards
M J
MJ
Lentsch
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AB
D000818:Animals; D054426:Chemokine CXCL2; D002630:Chemotactic Factors / Q000235:genetics; D004487:Edema; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D016753:Interleukin-10 / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D008102:Liver Circulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015427:Reperfusion Injury / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D054426:Chemokine CXCL2; D002630:Chemotactic Factors; D015846:Monokines; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10