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).
Alcohol abuse also leads to a significant elevation of activated CD8 T cells, measured by increased expression of human leukocyte antigen (HLA)-DR in adult males who consumed an average of 23 drinks/day for approximately 27 years that persisted for up to 10 days of abstinence (Cook, Garvey et al. 1991). Similarly, an increased percentage of CD8 T cells expressing HLA-DR and CD57 was reported in the group of male alcoholics with self reported average alcohol consumption of approximately 400g/day for approximately 26 years (Cook, Ballas et al. 1995). Mice that consumed 20% (w/v) ethanol in water for up to 6 months, also showed an increased percentage of activated T cells as measured by increased expression of CD43, Ly6C, rapid IFN-γ response, and increased sensitivity to low levels of TCR stimulation (Song, Coleman et al. 2002, Zhang and Meadows 2005). Taken together, these studies suggest that chronic alcohol-induced T cell lymphopenia increases T cell activation and homeostatic proliferation resulting in increased proportion of memory T cells relative to naïve T cells. In contrast to the inhibitory effects of acute alcohol treatment (up to 24 hours), prolonged exposure of human (men and women) peripheral blood monocytes to 25mM ethanol for 7 days increased LPS-induced TNF-α production without affecting IL-10 production (Pang, Bala et al. 2011).
Interplay Between Alcohol-Induced Stress & Immunity
As we said before, your immune system protects your body from unwelcome invaders and certain types of cancers. What’s more, a short period of binge drinking — let’s say a month — can cause a reduction in T cells. And this reduction is equal to that of someone who has been binge drinking for 6 months. Consuming alcohol likely slows your recovery since your immune system isn’t functioning at optimal levels when you are drinking. The bottom line is, it is best to avoid drinking during illness if you want to feel better quicker. Once you start drinking, your body has to work to metabolize the alcohol, since it considers ethanol a toxin.
Clinicians have long observed an association between excessive alcohol consumption and adverse immune-related health effects such as susceptibility to pneumonia. 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. Response to different stressors is mediated by several neural circuits that converge on the paraventricular nucleus (PVN) of the hypothalamus (Myers, McKlveen https://ecosoberhouse.com/ et al. 2014). The PVN regulates pituitary hormone production, including adrenocorticotropic hormone (ACTH), which binds to melanocortin type 2 receptors in the adrenal cortex to induce steroidogenesis in distinct layers (Dringenberg, Schwitalla et al. 2013). Primates have a threelayer adrenal cortex with cortisol being the primary glucocorticoid produced in the zona fasciculata (Nguyen and Conley 2008), which is released in response to stress (O’Connor, O’Halloran et al. 2000). Corticosterone is the main glucocorticoid involved in the regulation of stress responses in rodents (Smith and Vale 2006).
The Gastrointestinal Microbiome: Alcohol Effects on the Composition of Intestinal Microbiota
Some of these molecules can activate the vagus nerve or reach the brain and liver via systemic circulation. Alcohol consumption causes dysregulation in the intestinal microbiota, which leads to an alteration in this communication and subsequently causes alterations in brain and liver functions. In the human body, the gut represents the organ with the largest surface area (approximately 32 m2) [2] as well as the one with the highest number of microbes, especially in the colon, where the density of bacterial cells has been estimated at 1011 to 1012 per milliliter [3]. After a child reaches the age of three, the bacterial composition of gut microbiota remains reasonably stable and is unique to everyone depending on different factors like genetics, diet, and different environmental factors. A healthy gut microbiota is characterized by its richness and diversity in its composition [4]. Nevertheless, studies have shown that the normal gut microbiota comprises mainly Bacteroidetes and Firmicutes as the dominant phyla, followed by Actinobacteria and Verrucomicrobia.
- B cells mature into plasma cells that produce antibodies, also known as immunoglobulins (Ig), to eliminate extracellular microorganisms and prevent the spread of infection.
- These data indicate that reactive oxygen species (ROS) play an important role in inflammation, which is induced by chronic alcohol consumption [29].
- In such patients, alcohol impairs mucosal immunity in the gut and lower respiratory system.
- 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 study of Xiao et al. [52] transplanted microbiota in mice from alcoholic to healthy, developed emotional symptoms, such as anxiety, which occurs during abstinence.
The canonical NF-κB pathway is responsive to numerous different receptors such as TLR4, IL-1, TNFR, and T-cell receptors [40]. 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]. In an unstimulated milieu, the above mentioned p100 processing is inhibited by degradation of NF-κB-inducing kinase (NIK) [43]. Here, TRAF3 rapidly binds the newly synthetized NIK and induces its ubiquitylation by recruiting of E3 ligases cellular inhibitor of apoptosis (cIAP), needing TRAF2 as an adaptor molecule [44]. Upon activation, the TRAF2–TRAF3–cIAP complex is recruited to the TNFα receptors and its subsequent ubiquitylation and degradation lead to NIK accumulation [44,45].
Effects of Alcohol on Gut Microbiota
For example, in a model of lung infection, acute alcohol intoxication suppressed the production of certain chemokines (i.e., CINC and MIP-2) during infection and inflammation, thereby markedly impairing the recruitment of additional neutrophils to the site of infection (Boé et al. 2003). This defective neutrophil recruitment could be partially does alcohol weaken your immune system restored by localized chemokine administration (Quinton et al. 2005). 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.
