Imbalance of the Immune Response According to Alcohol Consumption Patterns

Alcohol intake promotes the translocation of endotoxins, stimulating immune cell activation and the production of cellular mediators, dysregulating the inflammatory process. We simultaneously evaluated the number of immune cells and cytokine concentrations, in relation to the pattern of alcohol consumption.

A cross-sectional study included five groups according to alcohol intake (hazardous drinking [HD], low alcohol use disorders [AUDs] [l-AUDs], moderate-severe AUDs [ms-AUDs], no decompensated cirrhosis, and alcohol-associated hepatitis [AH]). The control (CT) group was comprised of blood bank donors with an AUD Identification Test (AUDIT) <8 and occasional alcohol consumption of ≤10 g/day. Hematological and biochemical analyses were performed. Lymphocyte subsets (CD3⁺, CD8⁺, CD4⁺, natural killer [NK⁺], and NKT⁺cells) were determined using FACS analyses, whereas cytokine levels were determined using multiplex array technology. Multiple comparisons, Spearman correlations, calculated ratios, and receiver operating characteristic (ROC) curves were carried out.

A total of 780 subjects were enrolled and 427 were classified according to the alcohol consumption criteria. The ms-AUD group showed the highest levels of CD8⁺, NK, and NKT cells, whereas patients with cirrhosis had the lowest number of CD8⁺ subsets. AH displayed the highest number of neutrophils and cytokines. Moreover, lower levels of NK and NKT cells and upregulation of IL-6, CXCL-8, and TNF-α concentrations were observed, in accordance with alcohol intake (AH >cirrhosis > ms-AUD > l-AUD > HD).

The number of immune cells (CD4⁺, CD8⁺, NK, and NKT cells) and IL-6, CXCL-8, IL-10, and TNF-α cytokine concentrations can be used as differential diagnostic parameters for AUD and could be considered an important criterion for the treatment of alcohol-associated liver disease (AALD).