Opposing Effects of Alcohol on the Immune System PMC

PMNs produce a host of bacteria-killing (i.e., bactericidal) molecules (e.g., myeloperoxidase, defensins, azurophil-derived bactericidal factors, bactericidal permeability-increasing protein, cationic proteins, gelatinase, and lactoferrin). In addition, PMNs participate in the regulation of the local defense response by releasing signaling molecules called cytokines and chemokines (e.g., tumor necrosis factor [TNF]-α; interleukin [IL]-1β, IL-6, and IL-8; and macrophage inflammatory protein [MIP]-2). These molecules help recruit and activate additional PMNs as well as macrophages to the site of an injury or infection. It is now thought that alcohol-induced sterile danger signals contribute to the proinflammatory cytokine activation seen after chronic alcohol use in various organs (e.g., liver, intestine, and brain).

1. It is known that alcohol-mediated sensitization of immune cells to gut-derived LPS is a major component in the pathogenesis of alcoholic liver disease and alcoholic pancreatitis (Choudhry et al. 2002; Keshavarzian et al. 1994; Nolan 2010; Szabo et al. 2010, 2011).
2. For instance, diet is considered as one of the many drivers in shaping the gut microbiota across the lifetime.
3. And high fat diets over time can upset the balance of bacteria in your gut that can help immune response.
4. The innate immune system is activated when the involved cells recognize certain immune danger signals.
5. A study in rats has shown that only two weeks of alcohol administration disrupts the intestinal barrier and after two weeks more, liver injury occurs [62].

Even a single episode of binge drinking can have measurable effects on the innate immune system, inducing a transient proinflammatory state within the first 20 minutes after alcohol ingestion, followed by an anti-inflammatory state 2 to 5 hours after alcohol ingestion (Afshar et al. 2015). Alcohol abuse suppresses multiple arms of the immune response, leading to an increased risk of infections. The course and resolution of both bacterial and viral infections is severely impaired in alcohol-abusing patients, resulting in greater patient morbidity and mortality. Multiple mechanisms have been identified underlying the immunosuppressive effects of alcohol.

Dietitians recommend sticking to one drink per day for women or two drinks per day for men. According to Favini, a moderate amount of drinking — one drink per day for women, and two drinks per day for men per the United States Dietary Guidelines for Americans — is generally safe for people in good health and unlikely to have a negative health topics effect on their immune systems. Too much alcohol affects your speech, muscle coordination and vital centers of your brain. This is of particular concern when you’re taking certain medications that also depress the brain’s function. The intestinal microbiota (IMB) is the set of microorganisms that inhabit our intestines.

In fact, intestinal bacteria maintain immune and metabolic homeostasis, protecting our organism against pathogens. The development of numerous inflammatory disorders and infections has been linked to altered gut bacterial composition or dysbiosis. For instance, diet is considered as one of the many drivers in shaping the gut microbiota across the lifetime.

Finally, SCFAs have been shown to modulate immune inflammation responses in extraintestinal organs such as the brain, by acting on microglia and astrocytes. Many studies have evaluated the effects of chronic alcohol on adaptive immune responses, and this research is reviewed in more detail in the article by Pasala and colleagues in this issue. Chronic alcoholics have impaired T-cell responses; moreover, the balance between Th1 and Th2 responses is shifted toward a predominance of Th2-type responses (Fan et al. 2011; Lau et al. 2006; Szabo 1999). Consistent with this, chronic alcoholics exhibit an increase in IgA and a relative decrease in IgG antibodies, which play a role in antibody-dependent cell-mediated immune responses (Massonnet et al. 2009; Nouri-Aria et al. 1986). Other studies have noted a greater-than-normal abundance of Th17 cells in people with alcoholic liver disease (Lafdil et al. 2010; Ye et al. 2011).

Too Little Time Outdoors

Not only that, but their review of literature suggests drinking too much during a pandemic may put you at greater risk of infection. When the body detects a threat—such as pathogens (e.g., bacteria, viruses), chemical irritants, or damaged tissues from injury—it initiates an inflammatory response to eliminate the threat and promote healing. Alcohol use disorder (AUD) is a chronic brain condition characterized by continued alcohol consumption despite harmful consequences.

If you are struggling with alcohol use disorder or suspect you have an unhealthy relationship with alcohol, you are not alone. Healthy habits, such as being active, eating a balanced diet, and getting enough sleep, can keep your immune system strong. But unhealthy factors, like stress, smoking, or drinking alcohol, can be taxing for your immune system and make it harder for it to fight off infection. Fatty liver, early stage alcoholic liver disease, develops in about 90% of people who drink more than one and a half to two ounces of alcohol per day. So, if you drink that much or more on most days of the week, you probably have fatty liver.

Alcohol-Induced Modulation of the Host Defense Against Different Pathogens

Vitamin D deficiency results in reduced differentiation, phagocytosis and oxidative burst, by monocytes as well as defective bactericidal activity by keratinocytes (Fabri, Stenger et al. 2011, Djukic, Onken et al. 2014). Catalase is localized to peroxisomes and requires hydrogen peroxide to oxidize alcohol into water and acetaldehyde. Alcohol signs of alcoholism metabolism can also take place in the pancreas by acinar and pancreatic stellate cells, which contributes to the development of alcoholic pancreatitis (Vonlaufen, Wilson et al. 2007). Additional studies are required to fully understand the role of ethanol metabolites and adducts in the development of alcoholic liver injury and organ damage.

Alcohol consumption and immunity

The cell-mediated arm of the innate immunity is orchestrated primarily by granulocytes, monocytes/macrophages, dendritic cells, and natural killer (NK) cells. Granulocytes are white blood cells (i.e., leukocytes) that derive their name from the large granules that are visible when the cells are stained for microscopic analysis. They further are characterized by oddly shaped nuclei with multiple lobes and therefore also are called polymorphonuclear leukocytes (PMNs). These cells act as phagocytes—that is, they engulf pathogens and ingest them in a process called phagocytosis. In addition, they can excrete toxic substances from their granules that can kill pathogens.

Alcohol and the Immune System

Therefore, there is a pressing need for in depth studies that examine dose-dependent effects of chronic ethanol consumption on immunity in vivo to allow for the complex interactions between ethanol, its metabolites, HPA signaling, nutritional deficiencies, and the immune system. In contrast, level of anti-inflammatory protein adiponectin increased (Joosten, van Erk et al. 2012). Similarly, plasma adiponectin concentration was increased after 28 days of daily consumption of 450mL of red wine compared with dealcoholized red wine amongst 34 men, in the absence of changes in subcutaneous and abdominal fat contents as well as body weight (Beulens, van Beers et al. 2006).

These observations suggest that immune defects seen in individuals with AUD could also be mediated by nutritional deficiencies in addition to barrier defects and functional changes in immune cells. However, the contributions of each of these changes to increased susceptibility to infection in individuals with AUD remain to be determined. T and B cell activation in the presence of retinoic acid results in the up-regulation of gut-homing molecules and generation of IgA-secreting B cells (Mora, Iwata et al. 2008). Consequently, deficiency in vitamin A results in the impairment of mucosal responses (Mora, Iwata et al. 2008). Vitamin D has long been known to have a critical role in calcium and phosphorous homeostasis. In addition, antigen presenting cells convert vitamin D to 1,25(OH)2VD3, a physiologically active form of vitamin D that is highly concentrated in lymphoid tissues (Mora, Iwata et al. 2008) where it can modulate function of T and B cells which express vitamin D receptors.

In addition, animal studies have indicated that acute alcohol intoxication can decrease complement activation in response to tissue injury resulting from disruptions in blood supply (i.e., ischemic injury). In contrast, chronic alcohol intake can activate the complement response (Roychowdhury et al. 2009), both by inducing the biochemical pathways that lead to activation of the complement cascade and by suppressing processes to terminate or regulate the cascade (Bykov et al. 2007). The first line of host defense involves both structural (i.e., epithelial) cells and immune cells (i.e., macrophages and dendritic cells) at mucosal surfaces. The epithelial cells function as a physical barrier as well as regulators of the innate and adaptive immunity. Particularly important are the epithelial immune barriers of the reproductive, GI, and respiratory tracts. Several lines of evidence suggest that alcohol abuse significantly disrupts the GI and respiratory tract immune barriers.

It is also critical to take into consideration that the effects of ethanol on immune function in vivo could involve the actions of its primary metabolite, acetaldehyde. Therefore, intermittent explosive disorder symptoms and causes more studies looking at the effects of ethanol metabolites in vivo are needed. Acetaldehyde has also been shown to affect NFκB-induced cytokine production in various liver cells.

Finally, in relation to the effect of alcohol on neuroinflammation, a study by Lowe et al. showed an attenuation of alcohol-induced neuroinflammation after reducing the gut bacterial load, as a result of antibiotic treatment [115]. We could hypothesize that by reducing the gut bacterial load, lower amounts of bacterial components would reach the systemic circulation, leading to reduced activation of pro-inflammatory components. To elicit a response from the cell-mediated arm of the adaptive immunity, antigens need to be presented to the CD4+ and CD8+ T-cells. Studies in rodents found that chronic alcohol feeding can impair presentation of protein antigens in the spleen (Mikszta et al. 1995).

Chronic alcohol consumption also affects the NKT cell populations that play important immunoregulatory roles. Thus, alcohol consumption enhances immature NKT (iNKT) cell proliferation and maturation in the thymus and increases IFN-γ–producing iNKT cells (Zhang et al. 2015). In vivo activation of iNKT cells induces a Th1-dominant immune response and enhances the activation of DCs as well as NK cells, B cells, and T cells in alcohol-consuming mice (Zhang et al. 2015).

Finally, acetaldehyde disrupts intestinal epithelial barrier function and increases paracellular permeability which plays a crucial role in the pathogenesis of alcoholic liver disease by a tyrosine kinase-dependent mechanism (Sheth, Seth et al. 2004). Male rats on a liquid diet with 35% of calories coming from ethanol also showed enhanced mRNA half-life and protein expression of LPS-induced TNF-α by increasing TNF-α in liver monocytes/macrophages (Kishore, McMullen et al. 2001). It is important to highlight other components like polyphenols, antioxidants and vitamins present in beer or wineReference González-Gross, Lebrón and Marcos26, Reference Percival and Sims27, when studying the health effects of these beverages. Ethanol may be detrimental to immune cells due to the generation of free radicals during clearance; however, alcoholic beverages containing antioxidants should be protective against immune cell damageReference Percival and Sims27, Reference Fenech, Stockley and Aitken28.