Alcohol affects many organs, including the immune system, with even moderate amounts of alcohol influencing immune responses. Although alcohol can alter the actions of all cell populations involved in the innate and adaptive immune responses, the effect in many cases is a subclinical immunosuppression that becomes clinically relevant only after a secondary insult (e.g., bacterial or viral infection or other tissue damage). Alcohol’s specific effects on the innate immune system depend on the pattern of alcohol exposure, with acute alcohol inhibiting and chronic alcohol accelerating inflammatory responses. The proinflammatory effects of chronic alcohol play a major role in the pathogenesis of alcoholic liver disease and pancreatitis, but also affect numerous other organs and tissues. In addition to promoting proinflammatory immune responses, alcohol also impairs anti-inflammatory cytokines.
We chose pneumococcal infection because bacterial pneumonias are the most prevalent pulmonary complication in PLWHA (Wallace et al. 1993), and alcohol consumption is a well-known risk factor for bacteremic pneumococcal pneumonia in non–HIV- and HIV-infected populations (Nuorti et al. 2000). Along with possibly promoting viral transmission, studies indicate that alcohol use by people who are uninfected may make them more susceptible to infection. In sexual transmission, HIV is acquired across the penile, vaginal, cervical, or rectal mucosa, and the integrity of the epithelial barrier and the innate defenses within these microenvironments provide the critical first lines of defense against HIV.
Alcohol and Adaptive Immune Responses to HIV Infection
Interestingly, prolonged exposure (four to seven days) increases TNFα production in human monocytes upon LPS treatment, indicating that acute and chronic alcohol exert different effects [63]. This is supported by other mouse models of chronic alcohol consumption, showing that chronic use enhances the LPS-induced hepatic mRNA expression of TNFα, IL-6, and IL-10 [130]. Similar data are provided in human pathologies, which are caused by excessive or chronic alcohol consumption. Serum levels of pro-inflammatory cytokines TNFα, IL-6, and IL-1 are increased in patients with advanced alcoholic liver disease [131]. In patients admitted to hospital with acute alcoholic hepatitis, serum levels of IL-8, IL-4, and IFNγ are higher than age- and sex-matched control patients [132]. The severity of this alcohol-induced hepatitis directly correlates with cytokine concentration, yet they can normalize after recovery [133].
In male Sprague-Dawley rats which have been nourished with Sustacal liquid diet (Mead Johnson, Evansville, IN) supplemented with 36% alcohol for four months, PMNs isolated from blood samples have upregulated CD18 expression on neutrophils to double that of control rats [206]. Alcohol contains components such as ethanol and antioxidants and is considered as a complex modulator to the immune system (Barr et al., 2016). Several in vitro and in vivo studies have demonstrated that ethanol modulates the function of monocytes and dendritic cells (innate immune cells) in a dose- and time-dependent manner. For example, while acute high-level exposure to ethanol inhibits proinflammatory cytokine production, long-term moderate administration of ethanol stimulates the process. In addition, in vivo consumption of moderate doses of alcohol enhances phagocytosis and reduces inflammatory cytokine production whereas chronic consumption of large doses inhibits phagocytosis and production of growth factors. For cell-mediated and humoral immunity (adaptive immunity), chronic alcohol abuse significantly reduces both the number and frequency of T lymphocytes, resulting in an increased proportion of memory T cells relative to naïve T cells, which interferes the development of efficacious responses to infection and vaccination.
The Adaptive Immune Response
Extremely heavy drinking — about 30 drinks per day — can throw off the balance of immune system cells. Your immune system has several different cell types, each of which has a different but very important job to help keep you healthy. When someone is exposed to a virus, the body mounts an immune response to attack and kill the foreign pathogen. The spike in alcohol sales has alarmed health experts and officials around the world, who are concerned that increased drinking could make people even more vulnerable to the respiratory disease.
T and B cell activation in the presence of retinoic acid results in the up-regulation of gut-homing molecules and generation of IgA-secreting B cells (Mora, Iwata et al. 2008). Consequently, deficiency in vitamin A results in the impairment of mucosal responses (Mora, Iwata et al. 2008). Vitamin D has long been known to have a critical role in calcium and phosphorous homeostasis. In addition, antigen presenting cells convert vitamin D to 1,25(OH)2VD3, a physiologically active form of vitamin D that does alcohol suppress immune system is highly concentrated in lymphoid tissues (Mora, Iwata et al. 2008) where it can modulate function of T and B cells which express vitamin D receptors. Vitamin D deficiency results in reduced differentiation, phagocytosis and oxidative burst, by monocytes as well as defective bactericidal activity by keratinocytes (Fabri, Stenger et al. 2011, Djukic, Onken et al. 2014). Acetaldehyde is the toxic byproduct that contributes to tissue damage, alcohol dependence, and addiction (Zakhari 2006).