ABSTRACT
Moderate consumption of alcohol has been found to be consistently associated with reduced risk for fatal or nonfatal coronary heart disease (CHD) and consequently allcause mortality.1-3 Favourable effects on the lipid profile such as increased levels of highdensity lipoprotein (HDL) cholesterol, and on haemostatic factors explain only about half of the beneficial effect of moderate alcohol consumption on CHD risk4; thus other mechanisms must be involved in mediating this risk reduction. Since atherosclerosis shows several features of an inflammatory disease, recently an anti-inflammatory action of moderate alcohol consumption has been suggested as contributing to the observed reduction in CHD morbidity and mortality.5 Immunomodulatory effects of alcohol consumption have long been described.6 Excessive and chronic alcohol consumption can lead to infections with various pathogens.7 Moreover, alcoholic liver disease at different stages is associated with a complex immune response locally as well as systemically, such as immigration of inflammatory cells in the liver, increased levels of markers of the acute phase response and immunoglobulins, or alterations of the cytokine balance.8-10
This review summarizes the available evidence linking alcohol consumption with alterations of the immune system, focusing on recent findings and suggesting a causal link between moderate alcohol consumption and its effects on the immune system, cardiovascular disease morbidity, and mortality. Extensive overviews dealing specifically with the effects of alcohol on the immune system have been published elsewhere.8,11-13
7.2 ALCOHOL, “ALCOHOL-RELATED” DISEASES, AND ALL-
CAUSE MORTALITY
Alcohol consumption is associated with all-cause mortality in a U-or J-shaped manner. That means, consumption of moderate amounts of alcohol is associated with lower allcause mortality than abstention from alcohol or heavy drinking.14-16 This reflects different overlaying morbidity and mortality rates of diseases of various organ systems in human beings. In a recently published meta-analysis of 200 studies on known or presumed alcohol-related diseases, alcohol consumption was associated with higher risk for liver cirrhosis, neoplasms of the upper respiratory and digestive track, hemorrhagic stroke, and injuries in a dose-dependent manner. Weaker but still significant associations were found with chronic pancreatitis, hypertension, and hepatocellular carcinoma.17 There is also good evidence for an increased risk of cancers of the stomach, colon, rectum, female breast, and ovaries.17-19
7.3 ALCOHOL, PATTERN OF INTAKE, TYPE OF BEVERAGE, AND CORONARY HEART DISEASE MORBIDITY AND MORTALITY
Numerous epidemiological studies have shown that light to moderate drinkers of alcohol are at lower risk for fatal or nonfatal CHD than abstainers or heavy drinkers,1,2 resulting in reduced all-cause mortality among these individuals. A recent meta-analysis including 51 studies (43 of them prospective) estimated a 20% risk reduction for consumption of 0 to 20 g of alcohol per day compared to nondrinkers and some risk reduction up to 72 g of alcohol per day3 (see Figure 7.1). Besides the amount of alcohol consumed, drinking patterns seem to have an important effect on the association between alcohol and CHD.20,21 Regular consumption of moderate amounts of alcohol has been found to be associated with lower risk estimates for CHD as well as for extension of atherosclerotic heart disease, whereas binge drinking does not seem to be beneficial or even exerts an adverse effect.16,22-24 Some authors have suggested that, especially in the case of wine, other ingredients of alcoholic beverages than ethanol might at least in part
mediate the beneficial effects on CHD risk.25-28 However, in several studies a reduced risk of CHD has been reported for moderate consumption of wine, as well as for beer and spirits.4,28-30 Moreover, based on data from the Physicians’ Health Study, a significant interaction among alcohol consumption, HDL-cholesterol, risk reduction for CHD, and a polymorphism in the gene coding for the alcohol dehydrogenase type 3 (ADH3) has been demonstrated, indicating that ethanol itself is largely responsible for the effect observed but also suggesting that genetic factors may play an important role.31 The lower CHD risk in moderate drinkers has also been observed in a wide variety of patient populations including those with diabetes, hypertension, and prior myocardial infarction.32 The consistency of these findings and the growing evidence that alcohol might protect against CHD via higher levels of HDL cholesterol, antithrombotic actions, or reduced insulin resistance argue for a causal protective effect of moderate alcohol consumption.33-36
7.4 ATHEROSCLEROSIS AND INFLAMMATION
Inflammatory processes play a pivotal role in the initiation, progression, and the final thrombotic complications of atherosclerosis. Atherosclerotic lesions contain immune cells such as macrophages and T cells in abundance. In addition, elevated plasma levels of several markers of the inflammatory cascade have been shown to predict future risk of plaque rupture. Several recent reviews provide excellent insight into the inflammatory characteristics of atherosclerosis on a molecular level, both locally and systemically, and from the clinical and epidemiological perspective.37-40 Compelling evidence supports the notion that atherosclerosis is an inflammatory disease and links findings from epidemiological, interventional, and experimental studies bolstering the hypothesis that the association between alcohol consumption and CHD is at least in part mediated by immunomodulatory effects of alcohol.
