Moderate Drinking, Inflammation, and Liver Disease

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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.

Introduction

Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. Alcohol-induced reactive oxygen and nitrogen species, as well as inflammatory and genetic factors, contribute to the development and progression of ALD. In contrast to the effects on coronary heart disease, moderate alcohol consumption has no benefit for liver disease and may even cause liver disease in susceptible individuals. Activation of inflammatory pathways by long-term heavy alcohol intake, as opposed to attenuation of inflammation by acute moderate alcohol consumption, likely contributes to some of the organ-specific effects of alcohol.

Section snippets

Alcohol Consumption and Liver Disease

While multiple studies suggest a beneficial effect of moderate alcohol consumption on coronary heart disease, a linear correlation exists between the amount and duration of alcohol use and liver disease. In the Western world, up to 50% of cases of end-stage liver disease are related to alcohol use (1). The “threshold” of alcohol consumption associated with ALD depends on the daily amount and the duration of alcohol intake. Furthermore, gender difference is a major factor in ALD. In males, a

Mechanisms of Liver Injury and the Role of Inflammation in Alcoholic Liver Disease

The mechanisms by which alcohol consumption causes liver damage involves a number of physiological and biochemical changes that lead to liver pathology. Alcohol dehydrogenase (ADH) is the dominant enzyme in alcohol oxidation producing acetaldehyde, which is further oxidized to acetate by aldehyde dehydrogenase (ALDH). When tissue alcohol levels exceed 10 mmol/L concentration, the microsomal enzyme cytochrome P450 2E1 (Cyp2E) is induced and participates in alcohol metabolism. It has been

Different Regulation of Inflammatory Pathways by Acute and Chronic Alcohol Use

Increasing evidence suggests that in contrast to the proinflammatory activation in alcoholic hepatitis by chronic excessive alcohol consumption, acute alcohol administration has anti-inflammatory effects. Consistent with this notion, peripheral blood monocytes obtained from patients with alcoholic hepatitis spontaneously produced increased amounts of TNFα and responded to ex vivo LPS stimulation with increased TNFα levels 19, 28, while acute alcohol consumption in normal volunteers results in

Conclusions

Moderate alcohol use in the amount of 20 to 30 g/d for men and 10 to 15 g for women is likely to be safe for most individuals. Nevertheless, an individual's threshold for alcohol-induced liver disease depends on multiple susceptibility factors and coexisting liver conditions. The presumed “safe” limits of alcohol use, therefore, cannot apply to people with cofactors such as chronic viral hepatitis, obesity, hemochromatosis, and other factors that increase the susceptibility of the liver to

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