In addition to laboratory studies confirming the impact of alcohol consumption on the innate immune system, several studies have looked at how heavy drinking can alter plasma cytokine levels. To this end, one study analyzed IL-10, IL-6, IL-18, and tumor necrosis factor α (TNF-α) levels in 25 non-treating seeking heavy drinkers after they had consumed an alcoholic drink. The researchers reported significant reductions in the TNF-α levels three and six hours after the alcohol consumption. These results could support a role, via an anti-inflammatory mechanism, for moderate alcohol intake in cardiovascular disease (CVD) prevention. This outcome underscores the importance of taking into account the amount of alcohol consumption when evaluating the immune response. Therefore, further studies focused on drinking pattern are necessary to elucidate the effect of moderate alcohol consumption on the immune response.
- Too much alcohol affects your speech, muscle coordination and vital centers of your brain.
- When the body is unable to clear a pathogen, an infection can worsen and lead to more severe, life threatening complications.
- Though there’s still limited data on the link between alcohol and COVID-19, past evidence shows alcohol consumption can worsen the outcomes from other respiratory illnesses by damaging the lungs and gut, and impairing the cells responsible for immune function.
However, LPS increase was not found in the brain, suggesting that other ligands and/or alcohol itself may activate TLR4 (Alfonso-Loeches et al. 2010; Lippai et al. 2013b). (A) The innate immune response is a very fast, pathogen-non-specific, first line of defense mechanism. It is mainly composed of macrophages, dendritic and natural killer cells, as well as different forms of granulocytes.
The First Line of Defense: The Effects of Alcohol on Post-Burn Intestinal Barrier, Immune Cells, and Microbiome
Likewise, male rats fed an ethanol-containing liquid diet (8.7% v/v for up to 4 weeks) experienced a progressive loss of both CD4+ and CD8+ T cells (Boyadjieva, Dokur et al. 2002). Increased apoptosis of T and B lymphocytes isolated from the thymus, spleen, and lymph nodes of female mice was observed following 16 hour culture with 0.4%-2% ethanol, concentrations 5 to 25 times the definition of intoxication (Slukvin and Jerrells 1995). In contrast to these observations, moderate consumption of beer (330mL for women and 660mL for men) for 30 days resulted in a significant increase in the number of leukocytes, mature CD3+ T lymphocytes, neutrophils and basophils in women, while only basophils were increased in men (Romeo, Warnberg et al. 2007).
Impact of Chronic Inflammation on Health
DCs uptake antigens in peripheral tissues which leads to their maturation, and then travel to draining lymph nodes where they present them to T cells (Janeway 2008). Similarly, consumption of 10% (w/v) ethanol in tap water ad libitum for 2 days in mice resulted in decreased bone marrow DC generation, decreased expression of CD80 and CD86, impaired induction of T cell proliferation, and a decrease in IL-12 production (Lau, Abe et al. 2006). This increased susceptibility has been recapitulated in rodent models of chronic alcohol abuse. For instance, increased morbidity and mortality, pulmonary virus titers, and decreased pulmonary influenza-specific CD8 T cell responses were reported in female mice infected with influenza that consumed 20% (w/v) ethanol in their drinking water for 4–8 weeks (Meyerholz, Edsen-Moore et al. 2008). Likewise, higher pathogen burden and decreased CD8 T cell immunity was observed in female mice administered ethanol at 15% (w/v) for 5 days and challenged with Listeria monocytogenes (Gurung, Young et al. 2009). Similar results have been seen in SIV infection of male nonhuman primates (Bagby, Stoltz et al. 2003, Molina, McNurlan et al. 2006, Poonia, Nelson et al. 2006, Marcondes, Watry et al. 2008).
By illuminating the key events and mechanisms of alcohol-induced immune activation or suppression, research is yielding deeper insights into alcohol’s highly variable and sometimes paradoxical influences on immune function. The insights summarized in this issue of ARCR present researchers and clinicians with opportunities to devise new interventions or refine existing ones to target the immune system and better manage alcohol-related diseases. The first point of contact for alcohol after consumption is the gastrointestinal (GI) system before it is absorbed into the bloodstream. Here, alcohol can damage the epithelial cells, T-cells, and neutrophils in the GI tract, all of which can alter the gut barrier function and allow intestinal microorganisms to leak into circulation. “There is evidence that chronic alcohol use makes people more susceptible to respiratory viral infections,” said Jung, the NIAAA’s director of the Division of Metabolism and Health Effects. Unhealthy alcohol use includes any alcohol use that puts your health or safety at risk or causes other alcohol-related problems.
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This will leave you feeling badly dehydrated in the morning, which may cause a severe headache. Your liver, which filters alcohol out of your body, will be unable to remove all of the alcohol overnight, so it’s likely you’ll wake with a hangover. Weekly intimacy seems to help boost your immune system compared to those who have it less often. Couples who had sex more than twice a week had lower levels of IgA than those who had no sex at all. If you use it regularly, you may have the same breathing problems you can get from nicotine cigarettes.
Alcohol alters the makeup of your gut microbiome — home to trillions of microorganisms performing several crucial roles for your health — and affects those microorganisms’ ability to support your immune system. It seems that drinking alcohol may also damage the immune cells that line the intestines and serve as the first line of defense against bacteria and viruses. Alcohol-mediated effects on CD8+ T-cell function also have been linked to impaired immunity in the lung in response to influenza infection (Meyerholz et al. 2008). Whether the increased viral load measured in SIV-infected chronic alcohol-fed macaques can be attributed to diminished CD8+ T-cell function remains to be established (Bagby et al. 2006; Kumar et al. 2005). Both the innate and the adaptive immune response are critical for effective host defense to infectious challenges.
Alcohol’s Effects on Maturation and Development of Immune Cells From Precursors
These may include infections after surgery, traumatic injury, or burns; accelerated progression of HIV disease; adult respiratory distress syndrome and other opportunistic lung infections; and infection with hepatitis C virus, cirrhosis, or liver cancer (hepatocellular carcinoma). Several studies have also shown that the lungs are highly vulnerable to the effects of alcohol. For example, alcohol can reduce the ability of respiratory epithelium cells to remove mucous from the what is an alcoholic nose or drinker’s nose rhinophyma lungs, which can directly damage lung tissue and weaken the proper functioning of the lungs over time. Although this chronic weakening of lung function may not cause any immediate symptoms, these effects can manifest when a severe respiratory infection occurs. Although most research has focused on the effects of heavy alcohol consumption on the immune system, several studies have also confirmed that even moderate consumption can have significant effects on the immune system.
There is evidence in a number of physiological systems that binge alcohol intake complicates recovery from physical trauma (see the article by Hammer and colleagues). Molina and colleagues review research showing that alcohol impairs recovery from three types of physical trauma—burn, hemorrhagic shock, and traumatic brain injury—by affecting immune homeostasis. Their article also highlights how the combined effect of alcohol and injury causes greater disruption to immune function than either challenge alone. Alcohol acts as a catalyst for inflammation, triggering your body’s inflammatory response.
Numerous studies have demonstrated that ethanol, its metabolites, and alterations of the gut microbiome suppress intestinal tight junction protein expression [58,59,60,61] producing that the epithelial layer becomes leaky or “permeable”. Alcohol increased gut permeability affects mucosal immunity and allows the translocation of bacterial or some critical components of their membrane into the bloodstream [47], reaching other organs that can be damaged. LPS (lipopolysaccharide), Gram-negative bacteria membrane main product, and other bacterial metabolites reach the liver via the portal vein where they are enabled to induce the activation of the inflammatory processes. 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]. In the liver, gut-derived molecules interact with the hepatocytes, parenchymal cells, and immune cells causing injuries including hepatic steatosis, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma [63]. The dendritic cell (DC), which plays a critical role in T cell activation and initiation of adaptive immune responses, is another innate immune cell affected by ethanol.
Acute high dose exposures inhibit whereas long-term treatments stimulate proinflammatory cytokine production. In addition, in vivo consumption of moderate amounts enhances phagocytosis and reduces inflammatory cytokine production whereas chronic consumption of large doses inhibits phagocytosis and production of growth factors. Not only does the immune system mediate alcohol-related injury and illness, but a growing body of literature also indicates that immune signaling in the brain may contribute to alcohol use disorder. The article by Crews, Sarkar, and colleagues presents evidence that alcohol results in neuroimmune activation. This may increase alcohol consumption and risky decisionmaking and decrease behavioral flexibility, thereby promoting and sustaining high levels of drinking. They also offer evidence that alcohol-induced neuroimmune activation plays a significant role in neural degeneration and that the neuroendocrine system is involved in controlling alcohol’s effects on peripheral immunity.
For example, acute intoxication in humans with blood alcohol levels of 0.2 percent can severely disrupt neutrophil functioning and their ability to destroy bacteria (Tamura et al. 1998). Studies in laboratory animals have confirmed the adverse effects of acute alcohol exposure understanding powerlessness and acceptance in early recovery on pulmonary infections. Pneumoniae impaired lung chemokine activity in response to the infection, which resulted in reduced recruitment of immune cells into the lungs, decreased bacterial clearance from the lungs, and increased mortality (Boé et al. 2001; Raasch et al. 2010).
Alcohol affects many organs, including the immune system, with even moderate amounts of alcohol influencing immune responses. Although alcohol can alter the actions of all cell populations involved in the innate and adaptive immune responses, the effect in many cases is a subclinical immunosuppression that becomes clinically relevant only after a secondary insult (e.g., bacterial or viral infection or other tissue damage). Alcohol’s specific effects on the innate immune system depend on the pattern of alcohol exposure, with acute alcohol inhibiting and chronic alcohol accelerating inflammatory responses. The proinflammatory effects of chronic alcohol play a major role in the pathogenesis of alcoholic liver disease and pancreatitis, but also affect numerous other organs and tissues. In addition to promoting proinflammatory immune responses, alcohol also impairs anti-inflammatory cytokines.
Rodents have a much shorter life span and often require forced (i.e., not initiated by the animal) exposure to alcohol, which is stressful. Moreover, a recent systematic comparison examining gene expression changes found that temporal gene response patterns to trauma, burns, and endotoxemia in mouse models correlated poorly with the human conditions (Seok, Warren et al. 2013). Nonhuman primates, on the other hand, voluntarily consume different amounts of alcohol psychological vs physiological dependence and allow us to conduct studies in an outbred species that shares significant physiological and genetic homology with humans while maintaining rigorous control over diet and other environmental cues. Moreover, immune systems of several nonhuman primate species are similar to those of humans and these animals are susceptible to several clinically important pathogens making them a valuable model to study the impact of ethanol on immunity (Hein and Griebel 2003).
These mechanisms involve structural host defense mechanisms in the gastrointestinal and respiratory tract as well as all of the principal components of the innate and adaptive immune systems, which are compromised both through alcohol’s direct effects and through alcohol-related dysregulation of other components. Analyses of alcohol’s diverse effects on various components of the immune system provide insight into the factors that lead to a greater risk of infection in the alcohol-abusing population. Some of these mechanisms are directly related to the pathology found in people with infections such as HIV/AIDS, tuberculosis, hepatitis, and pneumonia who continue to use and abuse alcohol. To date, most studies have reported that heavy alcohol consumption directly alters the biodiversity of gut microbes and produces dramatic change in the relative abundance of some particular microbes, causing dysbiosis and inflammation in the gut [47,48,49]. Similar effects have been shown in moderate alcohol consumption and chronic consumption in animal models [46,50,51,52]. Unlike chronic alcohol consumption, binge drinking pattern (a frequent form of alcohol consumption, defined as 5 or more drinks for men and 4 or more drinks for women within 2 h) has not shown homogeneous results even using similar experimental designs.