A critical review of recent knowledge of alcohol's effects on the immunological response in different tissues

• Published in: Alcohol, clinical & experimental research clinical & experimental research, 2023-01, Vol.47 (1), p.36-44
• Main Authors: Crotty, Kathryn, Anton, Paige, Coleman, Leon G., Morris, Niya L., Lewis, Sloan A., Samuelson, Derrick R., McMahan, Rachel H., Hartmann, Phillipp, Kim, Adam, Ratna, Anuradha, Mandrekar, Pranoti, Wyatt, Todd A., Choudhry, Mashkoor A., Kovacs, Elizabeth J., McCullough, Rebecca, Yeligar, Samantha M.
• Format: Article
• Language: English
• Subjects: Alcohol use; alcohol use disorder; Alcoholism - metabolism; Alveoli; Drinking behavior; Ethanol - metabolism; Hepatocytes; Homeostasis; Humans; Immune response; Immune system; immunity; Inflammation; Kupffer cells; Liver; Lung; Macrophages; Macrophages, Alveolar - metabolism; Microglia; Morbidity; multi‐organ dysfunction
• ISSN: 0145-6008; 2993-7175; 1530-0277; 2993-7175
• DOI: 10.1111/acer.14979

Alcohol misuse contributes to the dysregulation of immune responses and multiorgan dysfunction across various tissues, which are associated with higher risk of morbidity and mortality in people with alcohol use disorders. Organ‐specific immune cells, including microglia in the brain, alveolar macrophages in the lungs, and Kupffer cells in the liver, play vital functions in host immune defense through tissue repair and maintenance of homeostasis. However, binge drinking and chronic alcohol misuse impair these immune cells' abilities to regulate inflammatory signaling and metabolism, thus contributing to multiorgan dysfunction. Further complicating these delicate systems, immune cell dysfunction associated with alcohol misuse is exacerbated by aging and gut barrier leakage. This critical review describes recent advances in elucidating the potential mechanisms by which alcohol misuse leads to derangements in host immunity and highlights current gaps in knowledge that may be the focus of future investigations. Alcohol use disorders cause multi‐organ damage, which are associated with high mortality and morbidity. Resident tissue immune cells are crucial in regulating tissue repair, yet immune defenses are impaired following alcohol misuse. This critical review highlights how chronic or binge alcohol impairs resident immune cell inflammatory signaling and metabolism, which can be exacerbated by multi‐organ crosstalk or aging. We aim to draw attention to potential mechanisms of host immune impairment and accentuate current gaps in knowledge for future investigation.