{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:33:36Z","timestamp":1791192816328,"version":"4.1.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4414,"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":[[2003,8]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The multifunctional cytokine interleukin 6 (IL\u20136) is expressed in a wide variety of disease states and pathologic processes. Mice deficient in IL\u20136 display abnormal and delayed liver regeneration and repair. Currently, IL\u20136 is thought to influence liver growth indirectly by priming hepatocytes to respond to growth factors such as hepatocyte growth factor (HGF) by inducing expression of HGF and by inhibiting hepatocyte apoptosis, as distinct from the direct mitotic effects of IL\u20136 on myeloid and other cell types. Here, we show that systemic administration of IL\u20136 using CHO cell tumors in nude mice results in dramatic hepatomegaly and hepatocyte hyperplasia in the absence of liver injury. Liver mass and liver to body mass ratios increased to 2 to 3 times normal because of proliferation of hepatocytes. Liver growth was associated with high levels of serum IL\u20136 and with activation of the IL\u20136\u2013signaling pathway, including increased expression of IL\u20136 receptor\u2013\u03b1\/gp80, activation of the signal transducer and activator of transcription\u20133 (STAT\u20133), and mitogen\u2013activated protein kinase (MAPK\/ERK)\u2013signaling pathways and induction of downstream target genes, including <jats:italic toggle=\"yes\">c\u2013myc<\/jats:italic>. HGF receptor and transforming growth factor \u03b1 (TGF\u2013\u03b1)\/epidermal growth factor (EGF) receptor activation were decreased in hypertrophied livers, suggesting that IL\u20136\u2013induced liver growth was independent of these known hepatocyte mitotic pathways. In conclusion, we suggest that IL\u20136 may function as a direct hepatic mitogen <jats:italic toggle=\"yes\">in vivo<\/jats:italic> and, furthermore, that IL\u20136 warrants closer examination as a potent liver growth factor with potential clinical utility for increasing liver mass following injury.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2003.50318","type":"journal-article","created":{"date-parts":[[2003,7,25]],"date-time":"2003-07-25T19:11:16Z","timestamp":1059160276000},"page":"326-334","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":121,"title":["Massive Liver Growth in Mice Induced by Systemic Interleukin 6 Administration"],"prefix":"10.1097","volume":"38","author":[{"given":"Teresa A.","family":"Zimmers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain 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