Increased toxin-induced liver injury and fibrosis in interleukin-6- deficient mice

Kellen Kovalovich, Robert A. Deangelis, Wei Li, Emma E. Furth, Gennaro Ciliberto, Rebecca Taub

Research output: Contribution to journalArticle

Abstract

Interleukin-6 null (IL-6-/-) mice have impaired liver regeneration and increased liver necrosis following partial hepatectomy that is corrected with IL-6 treatment. Following acute carbon tetrachloride (CCl4) treatment, we found that IL-6-/- mice developed increased hepatocellular injury and defective regeneration with significant blunting of signal transducer-and- activator of transcription protein 3 (STAT3) and nuclear factor-κB (NF-κB) activation and reduced hepatocyte DNA synthetic and mitotic responses. After CCl4 treatment, unlike partial hepatectomy, increased hepatocyte apoptosis was noted in IL-6-/- livers. Pretreatment with IL-6 before CCl4 reduced acute CCl4 injury and apoptosis and accelerated regeneration in both IL-6+/+ and -/- livers. Repetitive doses of CCl4 in the presence or absence of phenobarbital resulted in increased injury and fibrosis in IL-6-/- compared with +/+ livers. After acute and chronic injury, IL-6-/- livers showed the protracted presence of α-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 CCl4-induced acute and chronic liver injury and fibrosis.

Original languageEnglish
Pages (from-to)149-159
Number of pages11
JournalHepatology
Volume31
Issue number1
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Hepatology

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    Kovalovich, K., Deangelis, R. A., Li, W., Furth, E. E., Ciliberto, G., & Taub, R. (2000). Increased toxin-induced liver injury and fibrosis in interleukin-6- deficient mice. Hepatology, 31(1), 149-159.