Moderate Drinking, Inflammation, and Liver Disease

It is well known that heavy drinking increases the risk of alcohol-related liver disease (ALD). Female gender, hepatitis C or B, obesity, and other cofactors increase susceptibility to ALD, so “safe” levels of alcohol consumption in regard to ALD vary among individuals. Inflammation is one mechanism by which alcohol causes liver damage. Increasing evidence suggests that in contrast to the proinflammatory activation by chronic excessive alcohol consumption, acute moderate alcohol administration has anti-inflammatory effects. Long-term alcohol administration results in increased baseline nuclear regulatory factor κB (NF-κB) activation in the livers of mice; in contrast, acute alcohol administration in mice attenuates lipopolysaccharide (LPS)-induced NF-κB activation in the liver and serum tumor necrosis factor alpha (TNFα) induction. Consistent with this notion, peripheral blood monocytes from patients with alcoholic hepatitis spontaneously produce increased amounts of TNFα and respond to ex vivo LPS stimulation with increased TNFα levels, while acute moderate alcohol consumption in normal volunteers results in the attenuation of TNFα production by various stimulants and attenuates monocyte production of other proinflammatory cytokines. To date, no evidence for a beneficial role of the anti-inflammatory effect of acute moderate alcohol consumption on the liver has been demonstrated, but this may contribute to the effect of alcohol on other organ systems.

Key words: Alcohol Drinking, Alcoholic Liver Diseases, Inflammation

Selected Abbreviations and Acronyms: ADH, alcohol dehydrogenase, ALD, alcohol-related liver disease, ALDH, aldehyde dehydrogenase, ALT, alanine aminotransferase, Cyp2E, cytochrome P450 2E1, HBV, hepatitis B virus, HCV, hepatitis C virus, LPS, lipopolysaccharide, MCP-1, monocyte chemotactic protein 1, NF-κB, nuclear regulatory factor κB, ROS, reactive oxygen species, TNFα, tumor necrosis factor α