{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:46:27Z","timestamp":1791276387928,"version":"4.1.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5722,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,1]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Interleukin-6 null (IL-6\u2212\/\u2212) mice have impaired liver regeneration and increased liver necrosis following partial hepatectomy that is corrected with IL-6 treatment. Following acute carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) treatment, we found that IL-6\u2212\/\u2212 mice developed increased hepatocellular injury and defective regeneration with significant blunting of signal transducer-and-activator of transcription protein 3 (STAT3) and nuclear factor-\u03baB (NF-\u03baB) activation and reduced hepatocyte DNA synthetic and mitotic responses. After CCl<jats:sub>4<\/jats:sub> treatment, unlike partial hepatectomy, increased hepatocyte apoptosis was noted in IL-6\u2212\/\u2212 livers. Pretreatment with IL-6 before CCl<jats:sub>4<\/jats:sub> reduced acute CCl<jats:sub>4<\/jats:sub> injury and apoptosis and accelerated regeneration in both IL-6+\/+ and \u2212\/\u2212 livers. Repetitive doses of CCl<jats:sub>4<\/jats:sub> in the presence or absence of phenobarbital resulted in increased injury and fibrosis in IL-6 \u2212\/\u2212 compared with +\/+ livers. After acute and chronic injury, IL-6\u2212\/\u2212 livers showed the protracted presence of \u03b1-smooth muscle actin associated with activated stellate cells, indicating a disturbed response in wound healing that progressed to fibrosis. These data provide evidence for an important role for IL-6 in reducing CCl<jats:sub>4<\/jats:sub>-induced acute and chronic liver injury and fibrosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510310123","type":"journal-article","created":{"date-parts":[[2004,7,28]],"date-time":"2004-07-28T07:42:03Z","timestamp":1091000523000},"page":"149-159","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":252,"title":["Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice"],"prefix":"10.1097","volume":"31","author":[{"given":"Kellen","family":"Kovalovich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"DeAngelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma E.","family":"Furth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennaro","family":"Ciliberto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Taub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1002\/hep.510310123-BIB1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1126\/science.276.5309.60","volume":"276","author":"Michalopoulos","year":"1997","journal-title":"Science"},{"key":"10.1002\/hep.510310123-BIB2","doi-asserted-by":"crossref","first-page":"30429","DOI":"10.1016\/S0021-9258(18)43831-8","volume":"269","author":"Cressman","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.510310123-BIB3","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1002\/hep.1840210531","volume":"21","author":"Cressman","year":"1995","journal-title":"Hepatology"},{"key":"10.1002\/hep.510310123-BIB4","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1126\/science.274.5291.1379","volume":"274","author":"Cressman","year":"1996","journal-title":"Science"},{"key":"10.1002\/hep.510310123-BIB5","first-page":"g579","volume":"263","author":"Akerman","year":"1992","journal-title":"American Journal of Physiology"},{"key":"10.1002\/hep.510310123-BIB6","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1073\/pnas.94.4.1441","volume":"94","author":"Yamada","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1002\/hep.510310123-BIB7","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/hep.1840060108","volume":"6","author":"Berger","year":"1966","journal-title":"Hepatology"},{"key":"10.1002\/hep.510310123-BIB8","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/209036a0","volume":"209","author":"Slater","year":"1966","journal-title":"Nature"},{"key":"10.1002\/hep.510310123-BIB9","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0002-9440(10)65594-0","volume":"153","author":"Shi","year":"1998","journal-title":"Am J Pathol"},{"key":"10.1002\/hep.510310123-BIB10","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/0016-5085(95)90149-3","volume":"108","author":"Czaja","year":"1995","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.510310123-BIB11","first-page":"1577","volume":"152","author":"Yamada","year":"1998","journal-title":"Am J Pathol"},{"key":"10.1002\/hep.510310123-BIB12","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nm0497-409","volume":"3","author":"Kondo","year":"1997","journal-title":"Nat Med"},{"key":"10.1002\/hep.510310123-BIB13","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1126\/science.274.5288.782","volume":"274","author":"Beg","year":"1996","journal-title":"Science"},{"key":"10.1002\/hep.510310123-BIB14","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/376167a0","volume":"376","author":"Beg","year":"1995","journal-title":"Nature"},{"key":"10.1002\/hep.510310123-BIB15","first-page":"167","volume":"19","author":"Friedman","journal-title":"Seminars in Liver Disease"},{"key":"10.1002\/hep.510310123-BIB16","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0272-2712(18)30274-9","volume":"16","author":"Davis","year":"1996","journal-title":"Clin. 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