Alcohol and the Immune System Alcohol Research: Current Reviews

Pretreatment with G-CSF ameliorates alcohol-induced neutrophil dysfunction, including impairments in neutrophil recruitment and bacterial killing. Chronic alcohol consumption reduces B-cell numbers, decreases antigen-specific antibody responses, increases the production of auto-antibodies, and interferes with B-cell development and maturation. Similarly to the intestine, the lung epithelial barrier is affected by chronical alcohol abuse as well, contributing to the pathophysiology of acute respiratory distress syndrome or acute lung injury. In conclusion, alcohol can enable pathogens to enter the systemic blood flow, a process that may lead to an increased susceptibility of patients with infections. Furthermore, the induction of DAMPs in a sterile environment by alcohol should be a focus of further research, because, potentially, this may provide novel understanding of the chronic inflammation after alcohol consumption in case of no visible damage to organs. As discussed above in the gene expression studies, the mechanisms by which ethanol exerts dose-dependent effects on the immune system could also include modulation of the hypothalamic-pituitary-adrenal (HPA) axis, which tightly regulates the stress response, in turn affecting immunity.

For example, the acetaldehyde that is formed during alcohol metabolism can interact with other proteins in the cells, interfering with their function. Therefore, it is possible that acetaldehyde also interacts with antibodies and thereby may alter antibody responses; however, this remains to be established (Thiele et al. 2008). Similarly, more work is needed to determine whether alcohol inhibits specific aspects of B-cell differentiation, such as immunoglobulin class switching and cell survival. Several studies have also shown that the lungs are highly vulnerable to the effects of alcohol.

Impact of Alcohol Abuse on the Adaptive Immune System

Similarly, vitamin C, also an antioxidant, is important for phagocytic activity of neutrophils and monocytes, and enhances T cell responses (Strohle and Hahn 2009). Thiamine, also known as vitamin B1, contributes to the activation of T cells, suppresses oxidative stress-induced NFκB activation in macrophages, and serves as an anti-inflammatory factor (Manzetti, Zhang et al. 2014). Antigen-specific responses are decreased in folate-deficient humans and animals (Dhur, Galan et al. 1991). 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. Several lines of evidence show that the number and function of B-cells are reduced by chronic alcohol. For example, chronic alcoholics exhibit loss of B-cells in the periphery and a reduced capacity to generate protective antibodies (Cook et al. 1996).

  • Recent studies suggest that the increase in IgA levels may be mediated by an ethanol- induced elevation of the enzyme neuronal nitric oxide synthase (nNOS) in the animals’ intestine, because inhibition of nNOS before ethanol injection suppressed the IgA increase (Budec et al. 2013).
  • This cilia-desensitization effect is known as alcohol-induced cilia dysfunction (AICD).
  • HLAs are proteins found on the surface of various cells that present antigens to the TCR on T cells to induce an immune response.

More recent studies demonstrated that this rapid and transient alcohol-induced increase in NO levels was triggered by the alcohol-induced phosphorylation of heat shock protein 90 (HSP90) (Simet et al. 2013b). Upon phosphorylation, HSP90 increases its association with endothelial nitric oxide synthase (eNOS) in cilia, which then activates does alcohol suppress immune system the cyclase–kinase cascade, resulting in increased CBF (Simet et al. 2013b). These findings are counterintuitive to the conventional wisdom that alcohol interferes with lung host defenses because stimulation of CBF should protect the lung; however, the clinical observation is that heavy alcohol exposure impairs lung host defenses.

Alcohol’s Effects on the Immune Defense

The adaptive immune system can be subdivided into cell-mediated immunity, carried out by T cells, and humoral immunity, carried out by B cells. T cells expressing the CD4 T cell co-receptor are known as T helper cells and play a critical role in the activation and maturation of monocytes, cytotoxic T cells and B cells. T cells expressing the CD8 T cell co-receptor are known as cytotoxic T cells and eliminate host cells infected with intracellular pathogens as well as tumor cells. B cells mature into plasma cells that produce antibodies, also known as immunoglobulins (Ig), to eliminate extracellular microorganisms and prevent the spread of infection. The adaptive immune response can be distinguished from innate immunity by the capability of generating immunological memory, or protective immunity against recurring disease caused by the same pathogen (Janeway 2008). Monocytes and macrophages are leukocytes with a single-lobed nucleus that also act as phagocytes and which therefore also are called mononuclear phagocytes.

does alcohol lower immunity

Similarly, ONP cells isolated from newborn mice and cultured in vitro in the presence of 100 mM ethanol for 12 days failed to respond to IL-7 and commit to the B lineage, suggesting intrinsic defects (Wang et al. 2011). Additional investigations demonstrated that alcohol affects ONP cell differentiation into B lineage at a late stage by down-regulating the expression of several transcription factors (e.g., EBF and PAX5) and cytokine receptors, such as the IL-7 receptor (IL-7Ra) (Wang et al. 2009). Additionally, disregarding the specificity of the innate immunity, the influence of alcohol-induced oxidative stress on cardiovascular system has to be considered as well. Rats subjected to chronic alcohol consumption (4 g/kg/day for 12 weeks) exhibit a significant increase in blood pressure compared with controls [188].

The First Line of Defense: The Effects of Alcohol on Post-Burn Intestinal Barrier, Immune Cells, and Microbiome

Among other reactions, LPS injection normally triggers lymphocyte migration out of the circulation and into tissues and the lymphatic system (Percival and Sims 2000). In water- or wine-consuming mice, LPS injection, as expected, led to a 50 percent reduction in the number of lymphocytes in the peripheral blood, indicating their mobilization into tissues. In contrast, the ethanol-consuming mice exhibited no change in the frequency of certain circulating lymphocytes (i.e., CD3 cells) after LPS injection, suggesting that chronic alcohol consumption may potentially impair the ability of lymphocytes to migrate out of circulation (Percival and Sims 2000). One potential explanation for the lack of detrimental effects of wine in this experiment could be the presence of phytochemicals in wine that may be able to overcome ethanol’s harmful impact on immunity. In addition to reducing T-cell numbers, chronic alcohol exposure disrupts the balance between different T-cell types (i.e., T-cell homeostasis), leading to a shift toward a memory phenotype. Specifically, people who had consumed 30.9 ± 18.7 alcoholic drinks/day for approximately 25.6 ± 11.5 years exhibited a decreased frequency of naïve (i.e., CD45RA+) CD4 and CD8 T cells, as well as an increased frequency of memory T cells (i.e., CD45RO+) (Cook et al. 1994).

  • These cells circulate in the blood or reside in special lymphoid tissues (e.g., the spleen, lymph nodes, and tonsils), where they can encounter antigens and initiate an immune response.
  • This is in contrast to the non-canonical pathway, which is mostly activated by receptors from the TNFα receptor superfamily [41], including activator of nuclear factor kB [42].
  • Each T cell expresses a unique T-cell receptor (TCR) that confers specificity for one particular foreign molecule (i.e., antigen).
  • Mycobacterium tuberculosis, the agent responsible for TB, is transmitted when a person inhales microscopic airborne particles containing the organism (i.e., “droplet nuclei”) coughed up by someone with active TB disease, although prolonged exposure usually is necessary before an infection becomes established.
  • 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).

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. T cells circulating in the blood recognize phagocytes simultaneously displaying antigens and MHC proteins. The T cells bind to the phagocyte-bound antigens through the help of docking molecules, called T-cell receptors. The activated T cells multiply and begin secreting cytokines, which, in turn, activate cytotoxic T cells that can then recognize, bind to, and destroy cells infected by the invading bacteria.

During an overwhelming inflammatory response, however, neutrophils, lymphocytes, and other tissue cells also can be sources of inflammatory cytokines. Excessive levels of these cytokines may cause tissue damage, whereas reduced levels may result in an insufficient immune response. One of the central features of ARDS is an impaired barrier function of the alveolar epithelial and endothelial cells.3 Studies on the effect of alcohol alone on alveolar barrier function have revealed that chronic alcohol intake alters physical barrier properties within alveoli (Guidot et al. 2000). Interestingly, alveolar cells from ethanol-fed rats had increased expression of sodium channels in the membrane facing the interior of the alveoli (i.e., the apical membrane). However, these alcohol-fed rats had diminished airway clearance when challenged with saline, even in the absence of an inflammatory challenge (Guidot et al. 2000). These data suggest that the alveolar epithelium actually is dysfunctional after alcohol exposure, even though it seems normal and is able to regulate the normal air–liquid interface by enhancing sodium channels at the apical surface.

does alcohol lower immunity

Similarly, the immunological abnormalities observed after both chronic and acute alcohol consumption appear to be consistent with a decreased cell-mediated immunity characterized by reduced T-cell proliferation, accompanied by an enhanced humoral immunity marked by increased antibody levels. This shift in the immune response likely impairs the body’s defense against bacterial infections requiring a predominantly cell-mediated immune response, such as infections with M. Tuberculosis or Listeria monocytogenes, which are discussed in the section “Consequences of Alcohol’s Effects on the Immune System.” Alcohol’s effects on the antibody-producing B cells is discussed in more detail in the following section. Neutrophils are the earliest immune effector cells recruited to the site of inflammation during a bacteria-triggered inflammatory response. In the case of pneumonia, neutrophil recruitment to the lung is a critical early step in the host’s immune response.

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. Each of these events is mediated by the activation of nuclear factor kappa B (NFκB), which can be inhibited by alcohol consumption and thus prevent the production of pro-inflammatory cytokines.

does alcohol lower immunity

Alcohol also influences the functions of the lymphoid tissue and alter the activation, secretion, and functions of crucial immune cells called lymphocytes. An army of antibodies — Another subsystem of the immune system is called adaptive immunity. This generates “immune memory,” which ensures that the next time the body faces the same invader, the immune system is better equipped to take it down. Dipak Sarkar, an expert on alcohol metabolism and immunity, and professor at Rutgers University, tells Inverse that he advises skipping alcohol altogether during the Covid-19 pandemic.