# Imbalance of the Immune Response According to Alcohol Consumption Patterns

**Authors:** Moises Martinez-Castillo, Abigail Hernandez-Barragan, Daniel Santana-Vargas, Zaira Medina-Avila, Marisela Hernandez-Santillan, Adrian Flores-Sanchez, Itzel Altamirano-Mendoza, Fatima Higuera-De La Tijera, Aldo Torre-Delgadillo, Jaqueline Cordova-Gallardo, José Luis Pérez-Hernández, Gabriela Gutierrez-Reyes

PMC · DOI: 10.1155/mi/1693583 · Mediators of Inflammation · 2025-10-16

## TL;DR

This study shows how different levels of alcohol consumption affect immune cell counts and cytokine levels, which could help diagnose and treat alcohol-related liver diseases.

## Contribution

The study identifies specific immune cell and cytokine patterns associated with varying alcohol consumption levels and liver disease severity.

## Key findings

- The ms-AUD group had the highest CD8+, NK, and NKT cell levels, while cirrhosis patients had the lowest CD8+ cells.
- AH patients showed the highest neutrophil and cytokine levels, with elevated IL-6, CXCL-8, and TNF-α.
- Immune cell and cytokine profiles can serve as diagnostic markers for alcohol use disorders and AALD.

## Abstract

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).

## Linked entities

- **Proteins:** cd.3 (Cd.3 conserved hypothetical protein), CD8A (CD8 subunit alpha), CD4 (CD4 molecule), IL6 (interleukin 6), CXCL8 (C-X-C motif chemokine ligand 8), TNF (tumor necrosis factor), IL10 (interleukin 10)

## Full-text entities

- **Genes:** GGTLC4P (gamma-glutamyltransferase light chain 4 pseudogene) [NCBI Gene 729838] {aka GGT}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, LOC102724197 (inactive glutathione hydrolase 2) [NCBI Gene 102724197] {aka GGT2}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, KRT16 (keratin 16) [NCBI Gene 3868] {aka CK16, FNEPPK, K16, K1CP, KRT16A, NEPPK}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, FCGR3A (Fc gamma receptor IIIa) [NCBI Gene 2214] {aka CD16-II, CD16A, FCG3, FCGR3, FCRIIIA, FcGRIIIA}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}
- **Diseases:** compensated cirrhosis (MESH:D005902), autoimmune diseases (MESH:D001327), steatohepatitis (MESH:D005234), overweight (MESH:D050177), jaundice (MESH:D007565), diabetes (MESH:D003920), Lymphopenia (MESH:D008231), HD (MESH:D006816), Mental Disorders (MESH:D001523), central nervous system disorders (MESH:D002493), hepatitis A, B, and C (MESH:D006509), traumatic brain injury (MESH:D000070642), liver cirrhosis (MESH:D008103), Cirrhosis (MESH:D005355), hepatic insufficiency (MESH:D048550), variceal bleeding (MESH:D014648), telangiectasias (MESH:D013684), systemic infections (MESH:D012141), HD (MESH:D063425), chronic liver disease (MESH:D008107), inflammation (MESH:D007249), cirrhotic (MESH:D000094724), AUDs (MESH:D000437), mitochondrial (MESH:D028361), bacteria (MESH:C000719206), flu (MESH:D007251), alcohol problems (MESH:D019973), immune dysregulation (OMIM:614878), HIV (MESH:D015658), hepatocellular carcinoma (MESH:D006528), chronic disease (MESH:D002908), infectious diseases (MESH:D003141), DSM-IV (MESH:D006011), proinflammatory cytokines (MESH:D000080424), AALD (MESH:D008108), liver decompensation (MESH:D017093), hepatitis (MESH:D056486), DSM (MESH:D001714), CT (MESH:C536209), thrombocytopenia (MESH:D013921), gastrointestinal infection (MESH:D005767), AH (MESH:D006519), infection (MESH:D007239), toxicity (MESH:D064420), acute-on-chronic liver failure (MESH:D065290), anemia (MESH:D000740), ascites (MESH:D001201), AH (MESH:D007039), portal hypertension (MESH:D006975), alcoholic cirrhosis (MESH:D008104), ALD (MESH:D000326), encephalopathy (MESH:D001927), hypertension (MESH:D006973), cellular injury and death (MESH:D003643), nutritional deficiencies (MESH:D044342)
- **Chemicals:** BMS-986253 (MESH:C000709704), ethanol (MESH:D000431), pentoxifylline (MESH:D010431), EDTA (MESH:D004492), bilirubin (MESH:D001663), Alcohol (MESH:D000438), acetaldehyde (MESH:D000079), PBS (MESH:D007854), Glucose (MESH:D005947), LPS (MESH:D008070), phosphatidylethanol (MESH:C051521), Prednisolone (MESH:D011239), ABX (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12952229/full.md

## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12952229/full.md

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Source: https://tomesphere.com/paper/PMC12952229