Interleukin-1 inhibition facilitates recovery from liver injury and promotes regeneration of hepatocytes in alcoholic hepatitis in mice

Liver Int. 2017 Jul;37(7):968-973. doi: 10.1111/liv.13430. Epub 2017 Apr 27.

Abstract

Background & aims: Inflammation and impaired hepatocyte regeneration contribute to liver failure in alcoholic hepatitis (AH). Interleukin (IL)-1 is a key inflammatory cytokine in the pathobiology of AH. The role of IL-1 in liver regeneration in the recovery phase of alcohol-induced liver injury is unknown.

Methods: In this study, we tested IL-1 receptor antagonist to block IL-1 signalling in a mouse model of acute-on-chronic liver injury on liver inflammation and hepatocyte regeneration in AH.

Results: We observed that inhibition of IL-1 signalling decreased liver inflammation and neutrophil infiltration, and resulted in enhanced regeneration of hepatocytes and increased rate of recovery from liver injury in AH.

Conclusion: Our novel findings suggest that IL-1 drives sustained liver inflammation and impaired hepatocyte regeneration even after cessation of ethanol exposure.

Keywords: alcoholic liver disease; interleukin 1; interleukin 1 receptor antagonist; liver regeneration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute-On-Chronic Liver Failure / drug therapy*
  • Acute-On-Chronic Liver Failure / metabolism
  • Acute-On-Chronic Liver Failure / pathology
  • Acute-On-Chronic Liver Failure / physiopathology
  • Animals
  • Cell Proliferation / drug effects*
  • Disease Models, Animal
  • Female
  • Hepatitis, Alcoholic / drug therapy*
  • Hepatitis, Alcoholic / metabolism
  • Hepatitis, Alcoholic / pathology
  • Hepatitis, Alcoholic / physiopathology
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Interleukin 1 Receptor Antagonist Protein / pharmacology*
  • Interleukin-1 / antagonists & inhibitors*
  • Interleukin-1 / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver / physiopathology
  • Liver Regeneration / drug effects*
  • Mice, Inbred C57BL
  • Neutrophil Infiltration / drug effects
  • Recovery of Function
  • Signal Transduction / drug effects
  • Time Factors

Substances

  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1