title: Normal pharmacologically-induced, but decreased regenerative liver growth in interleukin-6-deficient (IL-6(-/-)) mice.
abstract: OBJECTIVE
  In the absence of liver damage, rapid liver growth can be induced pharmacologically by so-called primary liver growth promoters. The importance of the acute-phase cytokines interleukin-6 and tumor necrosis factor-alpha for the actions of these compounds is not clear. This study aimed to investigate the importance of IL-6 and TNF-receptor-1 in pharmacologically-induced liver growth.
  
  
  METHODS
  IL-6 knockout (IL-6(-/-)), TNF-receptor-1 knockout (TNFR1(-/-)) and wild-type mice were treated with the peroxisome proliferator nafenopin and the anti-androgen cyproterone acetate (CPA) in one single injection or for 6 days with daily injections, and examined at 24 or 48 h after treatment. In a control experiment, IL-6(-/-) mice were subjected to two-thirds partial hepatectomy.
  
  
  RESULTS
  Nafenopin treatment increased relative liver weight and DNA synthesis similarly in IL-6(-/-), TNFR1(-/-) and wild-type mice. CPA increased liver weight similarly in all groups, but did not increase DNA synthesis. Expression of peroxisome proliferator activated receptor-alpha mRNA was increased in both IL-6(-/-) and wild-type mice by nafenopin treatment, but not by CPA treatment. After hepatectomy DNA synthesis was suppressed in IL-6(-/-) mice compared to wild-type mice.
  
  
  CONCLUSIONS
  Liver growth induced by nafenopin and CPA was not dependent on the presence of IL-6 or TNF receptor-1, whereas liver regeneration was decreased in IL-6(-/-) mice.
authors.affiliation: Research Center for Endocrinology and Metabolism, Dept. of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. ville.wallenius@medic.gu.se
authors.forename: V
authors.initials: V
authors.lastname: Wallenius
authors.forename: K
authors.initials: K
authors.lastname: Wallenius
authors.forename: J O
authors.initials: JO
authors.lastname: Jansson
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D017373:Cyproterone Acetate / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D006498:Hepatectomy; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009255:Nafenopin / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D020025:Peroxisome Proliferators / Q000494:pharmacology; D011184:Postoperative Period; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D012016:Reference Values; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000726:Androgen Antagonists; D015703:Antigens, CD; D015850:Interleukin-6; D020025:Peroxisome Proliferators; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014157:Transcription Factors; D009255:Nafenopin; D017373:Cyproterone Acetate; D004247:DNA