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Endogenous IL‐13 protects hepatocytes and vascular endothelial cells during ischemia/reperfusion injury
Author(s) -
Kato Atsushi,
Okaya Tomohisa,
Lentsch Alex B.
Publication year - 2003
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2003.50075
Subject(s) - reperfusion injury , ischemia , endogeny , medicine , inflammation , liver injury , endothelial stem cell , proinflammatory cytokine , immunology , endothelium , extravasation , cytokine , endocrinology , pharmacology , biology , in vitro , biochemistry
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.