Inflammation in alcoholic liver disease

Annu Rev Nutr. 2012 Aug 21;32:343-68. doi: 10.1146/annurev-nutr-072610-145138. Epub 2012 Apr 18.

Abstract

Frank Burr Mallory's landmark observation in 1911 on the histopathology of alcoholic liver disease (ALD) was the first identification of a link between inflammation and ALD. In this review, we summarize recent advances regarding the origins and roles of various inflammatory components in ALD. Metabolism of ethanol generates a number of metabolites, including acetate, reactive oxygen species, acetaldehyde, and epigenetic changes, that can induce inflammatory responses. Alcohol and its metabolites can also initiate and aggravate inflammatory conditions by promoting gut leakiness of microbial products, by sensitizing immune cells to stimulation, and by activating innate immune pathways, such as complement. Chronic alcohol consumption also sensitizes nonimmune cells, e.g., hepatocytes, to inflammatory signals and impairs their ability to respond to protective signals. Based on these advances, a number of inflammatory targets have been identified with potential for therapeutic intervention in ALD, presenting new opportunities and challenges for translational research.

Publication types

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

MeSH terms

  • Animals
  • Antioxidants / therapeutic use
  • Humans
  • Immune System / drug effects
  • Immune System / immunology*
  • Immune System / metabolism
  • Immune System / pathology
  • Immunologic Factors / therapeutic use
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / therapeutic use
  • Liver Diseases, Alcoholic / drug therapy
  • Liver Diseases, Alcoholic / immunology*
  • Liver Diseases, Alcoholic / metabolism
  • Liver Diseases, Alcoholic / pathology

Substances

  • Antioxidants
  • Immunologic Factors
  • Inflammation Mediators