TNFR1 and TNFR2 levels in patients with severe alcohol use disorder undergoing withdrawal and their relationship with delirium tremens

Abstract

Background: Chronic alcohol consumption has been associated with cytokine dysregulation. Tumor necrosis factor-alpha (TNF-α), mediated through two distinct receptors-TNF receptor type 1 (TNFR1) and TNF receptor type 2 (TNFR2)-plays a role in alcohol use disorder (AUD). Evidence also suggests a potential role of TNFR1 and TNFR2 in delirium development. We aimed to investigate the role of TNFR1 and TNFR2 in patients with AUD undergoing withdrawal and the differences in these levels between those with and without delirium tremens (DT).

Methods: Ninety treatment-seeking patients with severe AUD and 117 healthy controls (HC) were enrolled and measured for blood levels of TNF-α, TNFR1 and TNFR2 using enzyme-linked immunosorbent assays. We followed the levels in AUD group after 2 weeks of withdrawal and categorized them based on the occurrence of DT (DT group, n = 19) and non-DT group (n = 71) during this period.

Results: At both week 0 and week 2, patients with AUD had higher plasma TNFR1, TNFR2, and TNF-α levels than healthy controls, with the DT subgroup showing greater elevations than the non-DT subgroup. Although levels declined after two weeks of alcohol withdrawal, they remained elevated compared to controls. Regression analysis indicated that age, sex, and TNF-α levels were significant contributors to TNFR1 and TNFR2 levels.

Conclusions: This study is the first to indicate that TNFR1 and TNFR2 levels were increased in patients with AUD but decreased, though not normalized, after early abstinence. DT subgroup is associated with more severe TNFR1 and TNFR2 dysregulation than non-DT subgroup.

Keywords: Alcohol use disorder; Alcohol withdrawal; Delirium tremens; Tumor necrosis factor receptor 1; Tumor necrosis factor receptor 2.