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). In fact, in acute alcoholic hepatitis, the severity of clinical outcome and death correlates with serum levels of the proinflammatory cytokines, particularly TNFα (Frazier et al. 2011; McClain et al. 2004). The exact triggers for alcohol-induced inflammation in the different tissues are yet to be identified.
This review will provide a summary of the current knowledge on the influence of alcohol consumption on certain factors of innate immunity after a hit, followed by the current studies that display the effect of alcohol with a description of the model, the mode of alcohol administration, as well as its dose. Future studies aimed at uncovering the mechanisms underlying dose-dependent modulation of immune function should also investigate changes in gene expression patterns, as well as factors that regulate gene expression including microRNAs and epigenetic changes within specific immune cell populations. Additionally, the role of alcohol-induced changes in the microbiome on immunity should be studied. Recent studies have shown that the microbiome modulates immunity in the gut, and in turn, immunity modulates the microbiome in the gut (Belkaid and Hand 2014). Only two studies have examined alcohol-induced changes in colonic (Mutlu, Gillevet et al. 2012) and fecal microbiomes (Chen, Yang et al. 2011), and both studies focused on individuals with AUD.
Modulation of Innate Immunity by Alcohol
It can also lead to a wide range of health problems, including high blood pressure and heart disease, liver disease, and increased risk of cancer. “By damaging those cells in your intestines, it can make it easier for pathogens to cross into your bloodstream,” says Nate Favini, MD, medical lead at Forward, a preventive primary care practice. That is, by drinking too much, you decrease your body’s defensive mechanisms to fight off a cold, virus, or other bacterial or viral infections.
For example, alcohol alters the numbers and relative abundances of microbes in the gut microbiome (see the article by Engen and colleagues), an extensive community of microorganisms in the intestine that aid in normal gut function. Alcohol consumption also damages epithelial cells, T cells, and neutrophils in the GI system, disrupting gut barrier function and facilitating leakage of microbes into the circulation (see the article by Hammer and colleagues). 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.
1. Cellular Responses—Phagocytosis and Oxidative Burst
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). In addition to direct induction of chemokines and most proinflammatory cytokines by TLR activation, activation of the inflammasome was detected in the liver, brain, and intestine after chronic alcohol use (Orman et al. 2013; Szabo and Lippai 2014). The inflammasome is a multiprotein intracytoplasmic complex that comprises a sensor (e.g., NLRP1, NLRP3, NLRC4, or a protein called AIM2) and adapter molecules (e.g., a molecule called ASC). This protein complex can be activated by a variety of sterile danger signals (Tsuchiya and Hara 2014). Activation of the inflammasomes results in induction of caspase-1, an enzyme needed to form mature secreted IL-1β or IL-18. Recent studies have demonstrated inflammasome activation and IL-1β induction in the liver, brain, and intestine after chronic alcohol administration in mice (Alfonso-Loeches et al. 2010; Lippai et al. 2013a,b, 2014; Orman et al. 2013).
- Pathways involving antigen presentation, B and T cell receptor signaling, and IL-15 signaling were altered with moderate vodka consumption (Joosten, van Erk et al. 2012).
- “Drinking alcohol in large quantities even just for a short period of time — like binge drinking — can be bad for your health and your immune system,” says Favini.
Sensitivity analysis removing palindromic SNPs (Table 1) revealed similar null associations for all autoimmune disorders. Mendelian randomization methods evaluate an overall casual estimation; it is likely that several distinct causal mechanisms underlie the alcohol–disease relationship, in which a risk factor influences outcome with different magnitudes of causal effect. We examined such a scenario through MR-Clust (Foley et al., 2019), an approach that divides IVs into distinct clusters such that all variants in the cluster have similar causal estimates. The correlation does alcohol suppress immune system between the genetic influences on a trait and the genetic influences on a different trait estimates the degree of causal overlap or pleiotropy. We quantified the genome-wide genetic correlation between alcohol consumption and each disorder, using an algorithm implemented in statistical software linkage disequilibrium score regression (LDSC). LDSC leverages the relationship between association statistics and linkage disequilibrium patterns across the genome and estimates the genetic correlation using only GWAS summary-level data (Bulik-Sullivan et al., 2015).
Drinking impairs immune cells in key organs
Although more studies are needed to define the mechanisms involved, it is increasingly clear that HIV and alcohol use may have synergistic pathology, resulting in greater rates of disease progression in HIV patients, fueled by the loss of intestinal mucosal cells and chronic immune activation due to microbial translocation. Because many of these same processes may also occur in rectal and genital mucosal tissues, HIV and alcohol use may interact similarly to increase susceptibility to HIV infection and early replication following sexual transmission, a proposition we examine below. Overall, studies of this kind find that CBA increases virus production in tissue and plasma of SIV-infected animals (Bagby et al. 2006; Kumar et al. 2005; Nelson et al. 2013; Poonia et al. 2005). In two separate studies (Bagby et al. 2006; Nelson et al. 2013), CBA/SIV infected rhesus macaques had higher viral set points than sucrose controls, and progressed faster to end-stage disease with a median survival time of 374 versus 900 days, respectively (Bagby et al. 2006). As expected, blood CD4+ lymphocyte numbers decreased during SIV infection but did not differ between CBA and sucrose-treated animals.
Genetically predicted levels of alcohol consumption and risk of common autoimmune diseases. GALT comprises both specialized regions of lymphoid tissues, called Peyer’s patches, and more diffuse lymphoid tissues scattered throughout the layer of the intestinal wall called the lamina propria. The specialized regions provide immune surveillance for the intestines and tend to initiate the gastrointestinal immune response. There is an even larger pool of differentiated T cells, called CD4+CCR5+ T cells, and plasma cells diffusely scattered throughout the intestine’s lamina propria that serve as the “effector” arm of the intestinal immune system, actively battling antigens first encountered by the Peyer’s patches (Mowat et al. 1997). In conclusion, alcohol influences the various components of the innate immunity in different directions depending on its dose and the duration of exposure. Summarized, despite numerous studies, yet little is known about its interactions on the human body.
Opposing Effects of Alcohol on the Immune System
The higher the viral load of the set point, the faster infection will progress to full-blown AIDS. 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. What’s more, a short period of binge drinking — let’s say a month — can cause a reduction in T cells. “Alcohol intake can kill normal healthy gut bacteria, which help to promote health and reduce risk of infection,” Mroszczyk-McDonald said. Similarly, alcohol can trigger inflammation in the gut and destroy the microorganisms that live in the intestine and maintain immune system health.