Hepatic Immune System: Adaptations to Alcohol

Handb Exp Pharmacol. 2018;248:347-367. doi: 10.1007/164_2017_88.


Both the innate and adaptive immune systems are critical for the maintenance of healthy liver function. Immune activity maintains the tolerogenic capacity of the liver, modulates hepatocellular response to various stresses, and orchestrates appropriate cellular repair and turnover. However, in response to heavy, chronic alcohol exposure, the finely tuned balance of pro- and anti-inflammatory functions in the liver is disrupted, leading to a state of chronic inflammation in the liver. Over time, this non-resolving inflammatory response contributes to the progression of alcoholic liver disease (ALD). Here we review the contributions of the cellular components of the immune system to the progression of ALD, as well as the pathophysiological roles for soluble and circulating mediators of immunity, including cytokines, chemokines, complement, and extracellular vesicles, in ALD. Finally, we compare the role of the innate immune response in health and disease in the liver to our growing understanding of the role of neuroimmunity in the development and maintenance of a healthy central nervous system, as well as the progression of neuroinflammation.

Keywords: Alcoholic liver disease; Cytokines; Hepatic macrophages; Innate immunity.

Publication types

  • Review

MeSH terms

  • Ethanol / pharmacology*
  • Humans
  • Immune System*
  • Immunity, Innate
  • Liver / drug effects*
  • Liver / immunology*
  • Liver Diseases, Alcoholic


  • Ethanol