The authors suggest that E-selectin may play an important role in neutrophil migration [203]. Furthermore, another chronic alcohol consumption model underlines a decrease of PMNs chemotaxis after LPS stimulation in alcohol-fed mice [204]. A further publication shows that alcohol may not only affect the general chemotaxis and migratory behavior of PMNs, but can modulate different steps of neutrophil infiltration in even contrasting directions as well [205].
- Tissue macrophages are given different names indicating their resident tissue such as Kupffer cells in the liver, microglia in the brain tissue, Langerhans cell in the skin, or alveolar macrophages in the lungs [156].
- In an in vitro model of acute inflammation, pretreatment of human lung epithelial cells with alcohol (85 or 170 mM) for 24 or 72 hours reduces IL-8 release upon their stimulation with IL-6.
- Perhaps the most dangerous effect is that alcohol use may affect the white blood cells in the body, which are responsible for getting rid of killer white blood cells.
- Together, these observations suggest that chronic alcohol consumption results in lymphopenia, which can increase homeostatic proliferation and accelerate conversion of naïve T cells into memory T cells (Cho et al. 2000).
These data underline not only the reduction of pro-inflammatory interleukins but an increase of anti-inflammatory cytokines in serum samples as well [129]. 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.
Modulation of Innate Immunity by Alcohol
More recent studies confirmed this observation and showed that the lack of lymphocytes (i.e., lymphopenia) was as severe in people who engaged in a short period of binge drinking as it was in individuals who drank heavily for 6 months (Tonnesen et al. 1990). Interestingly, abstinence for 30 days was sufficient to restore lymphocyte numbers back to control levels (Tonnesen et al. 1990). Similar findings were obtained in animal models, where the number of T cells in the spleen decreased in mice fed a liquid diet (i.e., Lieber-DeCarli diet) containing 7 percent ethanol for does alcohol compromise your immune system as little as 7 days (Saad and Jerrells 1991) or 6 percent ethanol for 28 days (Percival and Sims 2000). Likewise, adult male Sprague-Dawley rats consuming liquid diets containing up to 12 g ethanol/kg/day for 35 days exhibited significantly reduced absolute numbers of T cells (Helm et al. 1996). Alcohol abuse suppresses multiple arms of the immune response, leading to an increased risk of infections. The course and resolution of both bacterial and viral infections is severely impaired in alcohol-abusing patients, resulting in greater patient morbidity and mortality.
Several lines of evidence suggest that alcohol abuse significantly disrupts the GI and respiratory tract immune barriers. Recently, it was reported that a single episode of binge alcohol consumption in alcohol-experienced human volunteers (men and women) initially (within the first 20 min) increased total number of peripheral blood monocytes and LPS-induced TNF-α production when blood alcohol levels were ~130mg/dL. However, similarly to the in vitro studies described above, at 2 and 5 hours post-binge the numbers of circulating monocytes were reduced and levels of antiinflammatory IL-10 levels were increased (Afshar, Richards et al. 2014). Numerous sources of evidence gathered from experiments carried out in rodents show that modifications in the composition of gut microbiota impact in the brain functions and behavioral aspects [65], including the predisposition to high alcohol consumption [66]. Leclercq et al. [67] found a correlation between leaky gut and inflammation with modifications in scores of depression, anxiety and social interactions in alcohol craving. Along the same line, it has been shown that rats replicate several behavioral and biochemical alterations after stool transplantation from patients with depression and anxiety behaviors [68].
Mental health
The rest of the SCFAs reach the circulatory system via the superior or inferior mesenteric vein, reaching the brain and crossing the blood–brain barrier thanks to monocarboxylate transporters thus being able to act as signaling molecules between the gut and the brain [74]. Specifically, chronic alcohol consumption could reduce the SCFAs count through the reduction in some Firmicutes genera, such as Faecalibacterium and Ruminococcaceae, on which the production of SCFAs depends [75,76]. Furthermore, it has been described that alcohol consumption would also have effects on other microbiota derived metabolites, leading to increases in branched-chain amino acids [77] and peptidoglycans [78]. However, studies showing the effect of alcohol on these microbiota derived metabolites are scarce. In addition to these changes in cytokine function, investigators also have shown a contribution of barrier dysfunction to the postinjury increase in infections in intoxicated people (Choudhry et al. 2004). Thus, alcohol intoxication can suppress chemokine production and impair the expression of proteins that allow neutrophils to adhere to other cells at the site of infection, which also contributes to increased susceptibility to infection.
