Cytokines and the molecular mechanisms of alcoholic liver disease

Alcohol Clin Exp Res. 1999 Sep;23(9):1419-24.


This manuscript was given as a plenary lecture at the annual meeting of the Research Society on Alcoholism in July of 1999. It describes the general mechanisms by which tumor necrosis factor (TNF) alpha, an injury-related cytokine, promotes liver regeneration and then details how TNF-initiated hepatotrophic signals are inhibited by chronic ethanol consumption. There is evidence that chronic ethanol exposure impairs the TNF-dependent activation of stress-activated protein kinases and some of their targets, including the growth-stimulatory DNA binding protein, c-Jun. Ethanol exposure also prevents TNF from activating the redox-sensitive transcription factor, NF kappa B, in regenerating hepatocytes. These effects are followed by decreased hepatocyte proliferation, as well as by impaired induction of TNF-regulated survival factors, such as Bcl-xL, in the liver. Thus, chronic ethanol consumption may damage the liver by inhibiting the hepatotrophic and hepatoprotective actions of TNFalpha and other growth-regulatory cytokines.

Publication types

  • Lecture
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Central Nervous System Depressants / poisoning
  • Cytokines / physiology
  • Ethanol / poisoning
  • Humans
  • Liver / cytology
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases, Alcoholic / mortality
  • Liver Diseases, Alcoholic / physiopathology*
  • Tumor Necrosis Factor-alpha / physiology*


  • Central Nervous System Depressants
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Ethanol