{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T22:30:14Z","timestamp":1774564214320,"version":"3.50.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2004,2,1]],"date-time":"2004-02-01T00:00:00Z","timestamp":1075593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Circulating and hepatic interleukin (IL)-6 levels are strongly increased during clinical and experimental cholestasis. Cholestatic liver injury is associated with increased susceptibility to endotoxin-induced toxicity. To determine the role of IL-6 herein, extrahepatic cholestasis was induced by bile duct ligation (BDL) in IL-6-gene deficient (IL-6\u2212\/\u2212) and normal (IL-6+\/+) mice. BDL elicited increased levels of hepatic IL-6 mRNA and protein in normal mice. Hepatocellular injury 2 weeks after BDL was similar in IL-6\u2212\/\u2212 and IL-6+\/+ mice as demonstrated by clinical chemistry and histopathology. Administration of endotoxin to cholestatic mice 2 weeks after BDL was associated with enhanced cytokine release, severe liver damage, and death when compared with sham-operated mice. Effects of endotoxin were largely similar in sham-operated IL-6\u2212\/\u2212 and IL-6+\/+ mice, but cholestatic IL-6\u2212\/\u2212 mice were more susceptible to the toxic effects of endotoxin, as reflected by increased cytokine release, more profound liver injury and lung inflammation, and higher mortality. Although endogenous IL-6 is not important in the development of liver injury after experimentally induced obstructive jaundice, this cytokine plays an important role in decreasing hypersensitivity to endotoxin in cholestatic mice.<\/jats:p>","DOI":"10.1164\/rccm.200303-311oc","type":"journal-article","created":{"date-parts":[[2003,11,10]],"date-time":"2003-11-10T20:14:55Z","timestamp":1068495295000},"page":"413-420","source":"Crossref","is-referenced-by-count":27,"title":["Cholestatic Interleukin-6\u2013Deficient Mice Succumb to Endotoxin-induced Liver Injury and Pulmonary Inflammation"],"prefix":"10.1093","volume":"169","author":[{"given":"Miguel E.","family":"Sewnath","sequence":"first","affiliation":[{"name":"Departments of Surgery, Experimental Internal Medicine, Cell Biology and Histology, and Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"van der Poll","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Experimental Internal Medicine, Cell Biology and Histology, and Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelis J. 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