How Does Alcohol Consumption Affect the Immune System?

08 Jun How Does Alcohol Consumption Affect the Immune System?

Increased levels of CCL11, a potent chemokine for IgE-producing eosinophils, may be compensating the reduced IgE levels (Helms, Messaoudi et al. 2012). In contrast, level of anti-inflammatory protein adiponectin increased (Joosten, van Erk et al. 2012). Similarly, plasma adiponectin concentration was increased after 28 days of daily consumption of 450mL of red wine compared with dealcoholized red wine amongst 34 men, in the absence of changes in subcutaneous and abdominal fat contents as well as body weight (Beulens, van Beers et al. 2006). The innate cellular response, which is mediated primarily by monocytes/macrophages and neutrophils, involves the recognition, phagocytosis, and destruction of pathogens—processes essential to subsequent adaptive responses. Acute and chronic alcohol abuse can interfere with the actions of these cells at various levels. They produce immune molecules called antibodies or immunoglobulins that they can either display on their surface or secrete.

• As mentioned previously, alveolar macrophages are key components of both innate and acquired immunity against invading pathogens in the lung.
• RSV infection itself causes a significant loss of ciliated cells from the airway epithelium and the remaining cilia beat more slowly compared with control cells from uninfected epithelia (Slager et al. 2006).
• 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.
• These phagocytic cells ingest and clear inhaled microbes and foreign particles from the lungs.

In contrast, men who consumed a similarly moderate amount of beer for the same period exhibited a significant increase in basophils alone. Although the innate immune response is immediate, it is not specific to any given pathogen. Some of the most notable contributors to the innate immune response include natural killer (NK) cells, neutrophils, monocytes, macrophages, and dendritic cells (DCs). These cells carry immune proteins (i.e., antibodies, or immunoglobulins) on their surface that recognize and bind to antigens. Like T cells, each B cell also recognizes only one specific antigen and becomes activated when it comes into contact with it. Most activated B cells develop into so-called plasma cells, which secrete their antibodies into the blood or lymph.

Innate vs. adaptive immunity

Further, despite the increased intestinal permeability, bacterial overgrowth and compositional disbalance has been described. Patients with chronic alcohol overconsumption show lowered counts of protective gastrointestinal bacteria such as Lactobacillus, Faecalibacterium, or Bacteroidetes, whereby the pathogenic bacterial families such as Proteobacteria, Enterobacteriaceae, and Streptococcaceae were overrepresented [214]. 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]. The mentioned data in this review was collected via a systematic literature search conducted using PubMed and Google Scholar.

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]. IKKα is activated by this accumulation independently on trimerization with IKKβ and IKKγ, in contrast to the canonical pathway [46]. Active IKKα ensures the processing of p100 and is followed by translocation of p52–RelB heterodimer into the nucleus to finally modulate NF-κB gene expression [47]. Additionally, IKKα phosphorylates NIK and is thereby regulating itself via a negative feedback loop [47]. Over the long term, excess drinking can cause chronic systemic inflammation and impaired ability to defend against infections, Koob says.

Types of T Cells

VDR normally reduces expression of a signaling molecule called renin angiotensin (RAS) (Li et al. 2004). Lowered RAS levels in turn induce dysregulation of the mitochondria (Kimura et al. 2005) and enhance production of reactive oxygen species (ROS) that can damage various molecules in the cells (Iuchi et al. 2003). Naïve human T cells produce low levels of VDR, but expression is increased to moderate levels in does alcohol suppress immune system activated T cells (Irvin et al. 2000). Human T cells incubated in vitro with variable concentrations of ethanol (0, 10, 25, and 50mM for 24 hours) showed a reduced expression of the VDR, accompanied by increased expression of RAS and ROS as well as increased T-cell death (Rehman et al. 2013). Additional analyses demonstrated that ethanol exposure promoted apoptosis by inducing breaks in the DNA of the T cells.

• Increased apoptosis of T and B lymphocytes isolated from the thymus, spleen, and lymph nodes of female mice was observed following 16 hour culture with 0.4%-2% ethanol, concentrations 5 to 25 times the definition of intoxication (Slukvin and Jerrells 1995).
• The canonical NF-κB pathway is responsive to numerous different receptors such as TLR4, IL-1, TNFR, and T-cell receptors [40].
• Apart from behavioral effects as often observed in intoxicated individuals, alcohol consumption also leads to immunological modulation on the humoral and cellular levels.
• 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].
• Upon ethanol administration, the NF-κB–DNA binding increases and the transcription of various target genes is induced, including chemokines (CCL2), pro-inflammatory cytokines (TNFα, IL-1β, IL-6), and pro-inflammatory oxidases (NOX, COX, iNOS) or proteases (TACE, tPA) [48,49].
• This effect may contribute to lung injury in response to inflammation (Holguin et al. 1998).
• Conversely, miRNAs can inhibit the actions of the methylation machinery and expression of proteins involved in histone modifications as well as can interfere with the transcription of mRNAs.