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. 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.
Alcohol also impacts the function of immune cells of the central nervous system (CNS), particularly astrocytes and microglia. Their ability to serve as antigen presenting cells and produce cytokines in vivo has been controversial (Dong and Benveniste 2001). In vitro studies have shown that acetaldehyde modulates cytokine production by astrocytes in a dose-dependent manner (Sarc, Wraber et al. 2011). Specifically, 24 hours of exposure to both low (1mM) and high (5mM) concentrations of acetaldehyde stimulate IL-6 secretion, however, 7 days of exposure to the high concentration of acetaldehyde, significantly decrease IL-6 secretion (Sarc, Wraber et al. 2011). In contrast, both acute (24 hours) and prolonged (7 days) exposure to low and high concentrations of acetaldehyde reduce TNF-α secretion by primary rat astrocyte (Sarc, Wraber et al. 2011). These observations could explain why animals drinking moderately generated a more robust response to MVA vaccination compared to controls and animals that drank to intoxication since these factors are critical for lymphocyte proliferation, T cell activation and effector function, and immune cell recruitment.
How Alcohol Weakens Your Immune System
Untreated, the disease progresses over a few years to AIDS, leading to eventual death for most people. The disease is transmitted from infected to uninfected people through biological fluids containing the virus, most commonly through sexual contact but also through contaminated needles and other means. Since its discovery in the early 1980s, HIV infection has become a pandemic, causing an estimated 36 million deaths. The World Health Organization estimates that in 2012, of the 35 million people living with HIV/AIDS (PLWHA), 2.3 million were newly infected and 1.6 million died of AIDS-related causes despite increased availability of effective antiretroviral therapy (ART) (Joint United Nations Programme on HIV/AIDS 2013). For example, following an infectious challenge, acute alcohol can suppress alveolar macrophage expression of IL-23, which helps activate naïve T-cells to differentiate into Th17 cells (Happel et al. 2006). Similarly, as with the Th1 responses, alcohol inhibits the ability of dendritic cells to promote Th17 responses, thereby favoring Th2 responses (Heinz and Waltenbaugh 2007).
The disbalance of intestinal bacterial composition as well the disruption of epithelial integrity seems to not be affected by a single alcohol binge, suggesting that the saying “the dose makes the poison” is correct [215]. Beside the immune cells-mediated host defense, mucous epithelial cells provide a physical barrier and contribute to regulation of innate and as well adaptive immunity. In the last years, microbiota has been extensively studied regarding its impact on various diseases. There is also evidence that alcohol abuse disrupts those epithelial barriers in gastrointestinal and respiratory tracts.
Understanding alcohol and our immune system
In addition, they can excrete toxic substances from their granules that can kill pathogens. 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. A second study by Joosten et al. also analyzed gene expression profiles in PBMCs isolated from 24 healthy male subjects who consumed 50mL of vodka with 200mL orange juice or only orange twice daily for 4 weeks during dinner (considered to be moderate). 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).
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 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). The effects of both acute and chronic alcohol exposure on the immune responses in the lungs and thus on susceptibility to pulmonary infections are discussed in more detail in the article by Simet and Sisson. It is increasingly evident that sensitization of proinflammatory pathways to activation in monocytes and macrophages after chronic alcohol use has biological and clinical significance.
How your liver breaks down alcohol in your body
Following chronical excessive alcohol intake, the intestinal barrier becomes “leaky” by altered tight junctions of epithelial cells. On the one hand, alcohol impairs the trafficking of zona occludens (ZO)-1 and occludin, does alcohol suppress immune system both proteins of tight junctions [209]. On the other hand, patients with alcoholic liver disease display increased intestinal levels of miR-212 that in turn binds the ZO-1 mRNA and impedes its synthesis [210].
In line with these results, using the same binge drinking model, wild-type mice show decreased levels of IL-15, TNFα, IL-9, IL-1β & IL-1α, IL-13, IL-17, and IL-6, while IL-10 and MIP-2 are increased in the peritoneal lavage fluid [23]. However, this is not represented in each compartment of the body, as acute alcohol use may deter TNFα production in serum, but, on the other hand, bronchoalveolar lavage fluid TNFα levels in the mouse model were not altered at any time after infection [81]. Importantly, it adds another dimension to alcohol’s modulation of immunity, because the observed effects may be exclusive to the investigated location. In human monocytes treated with 25 mM alcohol, short term exposure (one to two days) reduces the LPS-induced TNFα release and gene expression.
How alcohol affects the innate immune system
DCs, which are the major cell type linking the innate and adaptive immune response, also are affected by alcohol intoxication. Acute alcohol exposure alters function and cytokine production in human monocyte-derived myeloid DCs (Szabo et al. 2004a). Chronic alcohol consumption in humans causes alterations in the immunophenotype of DCs and decreased production of IL-1β and TNFα (Laso et al. 2007). Studies in rhesus macaques have helped elucidate the effects of alcohol on DC development in hematopoietic tissues and the functional activities of the DCs (Siggins et al. 2009).
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. 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 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.
