Focus on: Alcohol and the immune system

Abstract

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. Multiple mechanisms have been identified underlying the immunosuppressive effects of alcohol. These mechanisms involve structural host defense mechanisms in the gastrointestinal and respiratory tract as well as all of the principal components of the innate and adaptive immune systems, which are compromised both through alcohol's direct effects and through alcohol-related dysregulation of other components. Analyses of alcohol's diverse effects on various components of the immune system provide insight into the factors that lead to a greater risk of infection in the alcohol-abusing population. Some of these mechanisms are directly related to the pathology found in people with infections such as HIV/AIDS, tuberculosis, hepatitis, and pneumonia who continue to use and abuse alcohol.

Figure 1

Alcohol’s effects on the structural host defense of the gastrointestinal (GI) tract. Alcohol-induced changes in tight junctions cause increased intestinal leaks that lead to translocation of bacteria-derived products such as lipopolysaccharide (LPS). These molecules enter the circulation to the liver where they activate endothelial and stellate cells as well as hepatocytes, resulting in a chronic inflammatory environment aggravating organ injury. This also may contribute to HIV disease pathophysiology. NOTE: CD14 = cluster of differentiation 14; HSC = hepatic stellate cell; IL = interleukin; NADPH = nicotinamide adenine dinucleotide phosphate; TGF= tissue growth factor; TNF = tumor necrosis factor; TLR4 = toll-like receptor 4.

Figure 2

Alcohol abuse decreases host defense against bacterial infections. In the lung, alcohol decreases barrier integrity, antioxidant capacity, chemokine and cytokine production and release in response to infection, and recruitment and activation of polymorphonuclear cells. Together, these defects in host response are associated with increased risk, morbidity, and mortality from infections in the alcohol-abusing host. NOTE: AE = alveolar epithelial; GM–CSF = granulocyte/macrophage-colony stimulating factor; ROS = reactive oxygen species; PMN = polymorphonuclear.

Figure 3

Biomedical consequences of alcohol-induced dysregulation of the immune system. These may include infections after surgery, traumatic injury, or burns; accelerated progression of HIV disease; adult respiratory distress syndrome and other opportunistic lung infections; and infection with hepatitis C virus, cirrhosis, or liver cancer (hepatocellular carcinoma).