title: Endogenous IL-13 protects hepatocytes and vascular endothelial cells during ischemia/reperfusion injury.
abstract: Hepatic ischemia/reperfusion injury involves a complex inflammatory cascade resulting in neutrophil-mediated injury of hepatocytes. Previous studies from our laboratory have established that exogenous administration of the anti-inflammatory cytokines interleukin 10 (IL-10) and IL-13 can ameliorate the inflammatory response and significantly reduce hepatocellular injury. The purpose of the present study was to determine if IL-10 and IL-13 function as endogenous regulators of the hepatic inflammatory response to ischemia/reperfusion. Wild-type, IL-10-, and IL-13-deficient (IL-10(-/-), IL-13(-/-)) mice were exposed to 90 minutes of partial hepatic ischemia and up to 24 hours of reperfusion. In wild-type mice, expression of IL-10 and IL-13 shared similar expression profiles with maximal production after 8 hours of reperfusion. There were no significant differences between wild-type and IL-10(-/-) mice in response to hepatic ischemia and reperfusion. IL-13(-/-) mice had much greater liver injury, as assessed biochemically and histologically, than wild-type mice. There were no differences between wild-type and IL-13(-/-) mice in their production of inflammatory cytokines, but IL-13(-/-) mice displayed disrupted neutrophil accumulation, with less neutrophils present in the hepatic parenchyma and far more neutrophils adherent to the endothelium of large hepatic venules than wild-type mice. These observations were associated with increased liver endothelial cell injury in IL-13(-/-) mice, as measured by serum levels of hyaluronic acid. In vitro, IL-13 protected hepatocytes from H(2)O(2)-induced cytotoxicity. In conclusion, IL-10 is not an important endogenous regulator of the inflammatory response to hepatic ischemia/reperfusion. In contrast, endogenous IL-13 appears to be critical for the control of this response, with prominent protective effects on hepatocytes and hepatic endothelial cells.
authors.affiliation: Department of Surgery, Division of Trauma and Critical Care, University of Cincinnati College of Medicine, OH 45267, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Okaya
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lentsch
mesh_terms: D000818:Animals; D019610:Cytoprotection / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008099:Liver / Q000503:physiopathology; D008102:Liver Circulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009504:Neutrophils / Q000502:physiology; D016877:Oxidants / Q000494:pharmacology; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
chemical_list: D018793:Interleukin-13; D016877:Oxidants; D016753:Interleukin-10; D006861:Hydrogen Peroxide