Alcohol has been widely used for its medicinal, antiseptic and analgesic properties, throughout human history. Nowadays, alcohol is a socially accepted substance and social drinking is a part of daily life in a large number of countries and societies.
Regarding immunity, researchers have long debated the effects of alcoholic beverage consumption on immune function. Generally, while high doses of alcohol consumption can directly suppress a wide range of immune responses, increasing the incidence of a number of infectious diseases, moderate alcohol consumption may have a beneficial impact on the immune system compared to alcohol abuse or abstinence(Reference Mendenhall, Theus and Roselle1–Reference Romeo, Wärnberg and Nova5). The relationship between alcohol exposure and either the potential health benefits or harm can eventually be considered multifactorial and depends on several factors(Reference Romeo, Wärnberg and Nova5).
Generally ‘social drinking’ refers to drinking patterns that are accepted by the society in which they occur and has often been confused with the concept of ‘moderate drinking’(6). However, social drinking may be neither moderate nor risk free; moderate drinking may be defined as drinking that does not generally cause health problems, either for the drinker or for society(6). Even though there is no universally accepted definition of ‘moderate consumption’, according to the literature, moderate alcohol consumption is considered to be no more than one drink per day for women and no more than two drinks per day for men(Reference González-Gross, Lebrón and Marcos7–9). While lacking an exact definition, social drinking usually takes place with two or more participants, is satisfying to the drinker and participants, and does not impede the drinker's health, interpersonal relations, or economic functioning(Reference Ewing10). As we will discuss later, the role of alcohol differs widely between different countries, societies and cultures(11). The aim of this review is to provide an overview of the immune aspects of social drinking.
Alcohol and the immune response
Alcohol abuse
Independent of social or cultural context, abusive alcohol consumption has a negative effect on organs and systems in the body, including the effects on the immune response(Reference Klatsky, Armstrong and Friedman12–Reference Kajander, Kupari and Laippala18).
Alcohol abuse seems to increase the incidence of a number of infectious diseases(Reference Ahmed19, Reference Szabo20) inducing functional abnormalities in several immune cells such as T-cells (e.g. a reduction in CD3+, CD4+ and CD8+ cell numbers)(Reference Boyadjieva, Dokur and Advis21) and B lymphocytes, natural killer cells and monocytes/macrophages, as well as altering cytokine production(Reference Deaciuc22–Reference Bautista24) and concentration (i.e. an increase of pro-inflammatory cytokines such as TNFα and IL-6(Reference Gonzalez-Quintela, Dominguez-Santalla and Perez25–Reference Szabo and Mandrekar27)). Moreover, high alcohol doses and abusive alcohol consumption lead to deterioration in both non-specific and cell-mediated immunity, independent of the alcoholic beverage type(Reference Romeo, Wärnberg and Nova5, Reference Romeo, Wärnberg and Nova28–Reference Schleifer, Keller and Shiflett30). The alcohol-induced specific changes on immune cell functions result in an inappropriate immune response to invading pathogens, leading to higher incidence of infections(Reference Szabo and Mandrekar27).
Ethanol
Although the harmful effects of alcohol abuse are well-documented, during the last decades researchers have been discussing how the consumption of alcoholic beverages may have a beneficial effect on host defence(Reference Diaz, Montero and González-Gross3, Reference Romeo, Wärnberg and Nova5). The main beneficial effect of moderate drinking on CVD prevention has generally been attributed to changes in the lipoprotein profile (mainly HDL-cholesterol), also reducing platelet aggregation and fibrinogen(Reference Frankel, Kanner and German31–Reference Romeo, González-Gross and Wärnberg36), independent of the type of alcoholic beverage consumed (liquor, beer, or wine), suggesting that this protective effect is due to ethanol itself(Reference Badía, Sacanella and Fernández-Solá37).
Some authors have highlighted the importance of the type of alcoholic beverage consumed and the amount of alcohol per se while evaluating the immune response, but this is still a matter of debate. Two decades ago, some researchers already indicated that alcohol per se has a significant negative effect on the non-specific cells of the immune system (basically a reduction of natural killer cell activity) in mice(Reference Poduval, Seshadri and Thakur38). Other animal studies have shown that the consumption of alcohol itself, even in moderate amounts, leads to lower levels of leucocytes(Reference Percival and Sims39), suggesting that alcohol can impair host defence to subsequent bacterial and viral challenges(Reference Szabo23). On the contrary, some authors have suggested that low ethanol intakes by the consumption of low amounts of distilled spirits, also show a stimulatory effect on cellular immune responses(Reference Mendenhall, Theus and Roselle1). In addition, results from an epidemiological study have suggested that ethanol itself might be largely responsible for the potential anti-inflammatory effects of moderate alcohol consumption, basically by a reduction of immune-related systemic inflammatory markers(Reference Imhof, Woodward and Doering40). Therefore, further research seems to be necessary to clarify the effects of alcohol itself on immunity.
Polyphenol-rich alcoholic beverages
Natural polyphenol compounds have been shown to possess different biological properties, such as anti-bacterial, anti-carcinogenic, anti-inflammatory, anti-viral, anti-allergic and immunostimulatory(Reference Larson41). Polyphenols are present in plants such as fruit, legumes, cereals, teas, herbs and spices(Reference Manach, Scalbert and Morand42). Specific fermented alcoholic beverages also contain numerous polyphenolic substances. For example, red wines contain many bioactive flavonoids and antioxidants(Reference de Lange and van de Wiel43) and beer contains phenolic compounds derived from hops and malts(Reference Kondo44). Several studies have stressed the importance of different active components contained in fermented alcoholic beverages such as wine or beer on immunity and inflammation, which may exert protective effects(Reference Romeo, Wärnberg and Nova5, Reference Gonzalez-Quintela, Dominguez-Santalla and Perez25, Reference Estruch35, Reference Percival and Sims39).
Although alcohol per se reliably increases HDL-cholesterol levels, other effects on oxidation, endothelial function and the immune response seem to be due to the substances prevalent in polyphenol-rich alcoholic beverages other than ethanol itself(Reference Romeo, Wärnberg and Nova5, Reference Frankel, Kanner and German31, Reference Estruch35, Reference Corder, Douthwaite and Lees45).
It is well established that alcohol consumption and its subsequent metabolism by the liver generates reactive oxygen species interfering with several immune cell functions(Reference Percival and Sims39). Some authors have suggested that phenolic antioxidants present in fermented alcoholic beverages such as red wine, may scavenge reactive oxygen species, preventing the impairment of immune cell functions, due to alcohol consumption(Reference Percival and Sims39, Reference Fenech, Stockley and Aitken46). Moreover, alcohol seems to enhance the bioavailability of these antioxidant components(Reference Rimm8, Reference Ghiselli, Natella and Guidi47).
It is important to keep in mind that those polyphenol-rich alcoholic beverages also contain significant amounts of other components such as vitamins and minerals that could be contributing to the preventing effect. To sum up, it is reasonable to suggest that the components of polyphenol-rich alcoholic beverages could contribute to the protective effect of moderate alcohol consumption on CVD and infection risk, representing a key to understanding the synergistic effect of both ethanol and these components.
Alcohol and inflammation
Inflammation plays a crucial role in both the initiation and progression of atherosclerosis and several types of immune cells including monocytes, macrophages, T lymphocytes and cytokines are involved(Reference Ross48). Evidence is growing that the protective CVD effects associated with moderate alcohol consumption are largely due to an anti-inflammatory effect(Reference Estruch35, Reference Stewart49–Reference Pai, Hankinson and Thadhani53).
Increased pro-inflammatory cytokines such as TNFα and IL-6 concentrations have frequently been found in alcoholic pathology(Reference Gonzalez-Quintela, Dominguez-Santalla and Perez25, Reference Daniluk, Szuster-Ciesielska and Drabko26). On the other hand, while a decrease in IL-10, IL-2 and interferon-γ levels have frequently been found in alcoholic pathology(Reference Gonzalez-Quintela, Dominguez-Santalla and Perez25, Reference Daniluk, Szuster-Ciesielska and Drabko26), moderate wine and beer consumption in human subjects has been shown to increase the production of anti-inflammatory IL-10 cytokine, also reducing some of the inflammatory mechanisms involved in atheromatous plaque formation(Reference Romeo, Warnberg and Nova4, Reference Badía, Sacanella and Fernández-Solá37).
Reviewing the literature, the relationship between the alcoholic beverage type and inflammation remains unresolved and requires further research. Moderate distilled alcohol consumption (2 ml vodka/kg body weight) has been suggested to show dual anti-inflammatory effects that involve IL-10 increase and a decrease of monocyte pro-inflammatory response that together support an anti-inflammatory mechanism for moderate alcohol intake in CVD prevention(Reference Mandrekar, Catalano and White54). Although some authors have suggested that the anti-inflammatory effect is attributed to alcohol itself(Reference Rimm, Giovannucci and Willet55), polyphenol-rich alcoholic beverages have shown a more pronounced anti-inflammatory effect than distilled spirits(Reference Estruch35, Reference Badía, Sacanella and Fernández-Solá37, Reference Ghiselli, Natella and Guidi47, Reference Villarino, Posada and Martínez56, Reference Vázquez-Agell, Sacanella and Tobias57). In this direction, previous animal studies showed the strong anti-inflammatory activity of some compounds presented in fermented alcoholic beverages, such as resveratrol in red wine(Reference Jang, Cai and Udeani58). In conclusion, different types of alcoholic beverages all seem to have the same inhibitory effect on inflammatory response(Reference Romeo, Wärnberg and Nova5, Reference Estruch35, Reference Mandrekar, Catalano and White54, Reference Winkler, Wirleitner and Schroecksnadel59), but further investigation into the specific effects of alcohol on inflammation functions should help to define the potential inflammatory effects of social drinking(Reference Szabo and Mandrekar27).
Drinking pattern
Epidemiological studies have demonstrated that there is a J-shaped relationship between alcohol intake and total mortality, but there may be differences in the strength of this relationship across the main categories of alcoholic beverages: beer, wine and distilled spirits(Reference Gronbaek60). While wine is commonly believed to confer the most protection against total mortality, distilled spirits are believed to confer the weakest protection(Reference Ferreira and Willoughby61). There is emerging evidence that the pattern of drinking (i.e. drinking with meals, abstention, followed by binge drinking) and the alcoholic beverage type influence the impact of the overall alcohol consumption on immunity, morbidity and mortality(Reference Romeo, Wärnberg and Nova5, Reference Ferreira and Willoughby61).
According to WHO, countries have been classified into four score categories (1 to 4) reflecting the mortality and morbidity risk associated with different amounts of alcohol intake. For example, category 1, characterized by the least-risky drinking pattern (light to moderate alcohol consumption with meals and without heavy drinking bouts) is associated with a lower burden of mortality and morbidity. On the contrary, category 4 is the most-risky drinking pattern characterized by the highest level of irregular drinking and is associated with a high burden of morbidity and mortality(Reference Rehm, Taylor and Patra62). The least-risky categories (1 and 2) were associated with the consumption of fermented beverages such as wine and beer, whereas the most-risky categories (3 and 4) were associated with the consumption of distilled spirits.
Therefore, according to Fig. 1, an emerging approach to the study of social drinking on mortality and disease burden in populations is to consider both the volume and pattern(Reference Ferreira and Willoughby61). On the other hand, there are also several lifestyle factors such as cultural, socio-economic status, diet and physical activity habits that must be taken into account to elucidate the global effects of alcoholic beverages on health and immunity(Reference Romeo, Wärnberg and Nova5, Reference Gronbaek60).
Fig. 1. Drinking pattern and lifestyle risk.
Social and cultural aspects of drinking
From the earliest times to the present, alcohol has played an important role in society. It is important to remember that alcohol has significant social consequences in most societies by way of celebration, stress reduction, appetite improvement, social interaction enhancement and feelings of well-being(Reference Peele and Brodsky63).
There is, however, a lack of an exact definition of ‘social drinking’; while in some societies alcohol consumption is associated with some related problems such as violence or anti-social behaviour, in others (such as the Mediterranean), drinking is accepted and even associated with health-related benefits. These differences are primarily determined by social and cultural factors, rather than the different levels of consumption or genetic differences(Reference Peele and Brodsky64). For example, the traditional Mediterranean diet has long been praised for its health benefits, which are characterized by high consumption of vegetables, fruits, nuts, legumes, cereals, seafood and olive oil, along with a moderate amount of red wine or beer(Reference Trichopoulou, Lagiou and Kuper65). Moreover, even total abstention from alcohol may be associated with health risks(66).
Some decades ago, cultural and socio-demographic differences were reported in the association between moderate alcohol consumption and CVD protection(Reference Keys67). Since the protective effect of alcohol consumption has been found to be greater for populations studied in the Mediterranean countries than in other countries(Reference Anderson68), it is reasonable to suggest that social, as well as cultural aspects influence the effects (positive or negative) derived from alcohol consumption. Moreover, since there has been an increased interest in how genes regulate alcohol drinking and contribute to alcoholism, we cannot forget the genomic or epigenetic basis and influence of these effects of alcohol consumption on highly regulated cellular pathways(Reference Pignataro, Varodayan and Tannenholz69).
Regarding drinking pattern and worldwide distribution (Fig. 2), curiously the drinking pattern classified as least-risky (described earlier as light to moderate; category 1) has been found only in Europe, Australia and Japan(Reference Rehm, Taylor and Patra62, Reference Rehm, Room and Graham70). On the contrary, the most-risky drinking pattern associated with a high burden of morbidity and mortality was found in Central America (for example, Guatemala and Nicaragua)(Reference Rehm, Taylor and Patra62, Reference Rehm, Room and Graham70).
Fig. 2. Drinking pattern and worldwide distribution (from Rehm et al.Reference Rehm, Taylor and Patra62, Reference Rehm, Room and Graham70).
Even among the countries with least risk of morbidity and mortality, the social context seems to be a determining factor while examining the effects of alcohol consumption on health. A recent prospective study conducted in Japan (19 356 men, 40–69 years of age) examined the effects of social support on the relationship between drinking and CVD, finding that the health benefits of light-to-moderate drinking (less risk of mortality and CVD) are more pronounced in men with greater social support(Reference Iso and Tanigawa71). The authors found that those subjects with low social support had more unhealthy lifestyles and mental stress which activates neuro-endocrine components including the hypothalamic–pituitary–adrenal-axis and the autonomic nervous system, which lead to an increased risk of CVD.
It has been also suggested that the prevalence of alcohol-related problems is not directly related to average per capita consumption. While countries with low average consumption (such as Ireland and Iceland) often register relatively high rates of alcohol-related social and psychiatric problems, others countries with much higher levels of consumption (such as France and Italy) score low on most indices of problem drinking(Reference Peele and Brodsky64).
Since social behaviours including drinking may have their origins in adolescence, special attention focused on this risk population is necessary(Reference Droomers, Schrijvers and Casswell72). The relevance of parental supervision has been underscored for increased educational achievement, and has been associated with a reduced risk of alcohol-related problems in adolescents(Reference Fothergill and Ensminger73).
Summary
Although research evidence supports the benefits of moderate alcohol consumption on health, the scientific literature also appears to be concerned about the diseases associated with excessive drinking in some societies and cultures(Reference Health74).
This review recognizes the importance to consider social aspects of drinking while examining the whole dimension of alcohol consumption (amount, beverage type, frequency and variability), in order to estimate the global risk of consequences on the host defence to better understand alcohol-related harm or benefit(Reference Rehm, Room and Graham70, Reference Health74, Reference Bobak, Room and Pikhart75) (Fig. 3).
Fig. 3. Relationships between drinking pattern and socio-cultural context on disease, mortality and host defence global risk.
A more flexible approach to alcohol policy development which emphasizes patterns of drinking and educational measures within their appropriate cultural context is still necessary(66). Lastly, though light-to-moderate alcohol consumption can be part of a healthy lifestyle for those who choose to consume alcohol, consumers must keep in mind that alcohol abuse is still considered as a major public health and social problem, the consequences of which extend beyond the subjects directly involved(Reference Russell, Light and Gruenewald76). A specific prevention for adolescents should play the most important role in a comprehensive plan to reduce alcohol-attributable burden(Reference Rehm, Taylor and Patra62). Educational approaches may be used in order to reduce alcohol-related harm, including education of children and adolescents in school, the development of drinking guidelines, labelling of alcoholic beverage products with warnings; school-based activities carried out as part of school plus family initiatives and as part of community action projects.
Acknowledgements
J. R., J. W. and A. M. declare no conflict of interest. All authors participated in the writing of the paper and provided comments on the drafts and approved the final version.
