Inflammatory Biomarkers for Personalizing Therapy in Alcohol Use Disorders

This study evaluated the potential of inflammatory biomarkers to enable personalized therapy in alcohol use disorders (AUDs), including alcohol withdrawal syndrome (AWS). We conducted a targeted review of clinical studies, systematic reviews, and meta-analyses identified in PubMed, Scopus, and Web of Science from January 2000 through July 2025. The most consistently replicated indicators were interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-18 (IL-18), and markers of endotoxemia. Elevations in these markers during chronic alcohol use and early abstinence are associated with greater AWS severity, increased risks of delirium and seizures, sleep disruption and cognitive deficits, infectious complications, and poorer one-year survival. Over 1–4 weeks of abstinence most pro-inflammatory measures decline, although several remain elevated. CRP modifies both clinical and neuroimaging responses to therapy with a neuroimmune mechanism of action; peripheral CRP correlates with the frontal choline signal on proton magnetic resonance spectroscopy (^1H-MRS) and predicts short-term consumption. An increased proportion of rapid eye movement (REM) sleep is linked to TNF-α activity and precedes relapse. Immunogenetic variation (e.g., IL17RB and components of the NF-κB pathway) is associated with response to maintenance pharmacotherapy (acamprosate) and risk of resumption of drinking. The collective evidence supports the use of biomarker panels for early risk stratification, monitoring the quality of remission, selection for immuno-targeted interventions, and correction of intestinal permeability. Limitations of the evidence base include small and heterogeneous samples and insufficient standardization of biomarker panels; large, carefully phenotyped longitudinal studies are warranted.