TNFR2 LEVEL CHANGES IN PATIENTS WITH ALCOHOL DEPENDENCE DURING EARLY WITHDRAWAL

Abstract Background Alcohol Withdrawal Syndrome (AWS) is one of the defining characteristics of alcohol dependence (AD) and can manifest with various clinical features, including delirium tremens (DTs), which is recognized as a severe form of AWS. Cytokine receptors like tumor necrosis factor receptor 2 (TNFR2) can mediate anti-apoptotic signals. Knockout studies in mice suggest a role of TNFR2 in protecting neurons from apoptosis by stimulating antioxidative pathways. Previous studies found that TNFR2 levels were elevated in alcoholic patients. This research sought to explore differences in TNFR2 levels between individuals with AD experiencing early withdrawal and healthy controls (HC). Methods We recruited 224 patients diagnosed with AD based on DSM-IV criteria, along with 117 healthy control (HC) participants. Within the AD group, 25 participants exhibited DTs (DT group). Blood samples were obtained from the AD group on the first day of withdrawal, as well as from the HC group. Enzyme- linked immunosorbent assays were utilized to measure serum levels of TNFR2. Results Patients with AD at baseline exhibited significantly elevated TNFR2 levels compared to HC. We observed the highest TNFR2 levels in the DT group (4362 pg/ml), followed by non-DT group (3175 pg/ml), and then the HC group (2157 pg/ml) (p<0.0001). The differences remain significant even after adjusting for education years and smoke package-years in the linear regression analysis. In addition, the multiple linear regression analysis demonstrated significant correlations between TNFR2 levels and age, smoking history, and alcohol consumption variables. Conclusion Our findings indicate that the dysregulation of immunocytokines could be linked to the underlying mechanisms of AD. In addition, the differential TNFR2 levels between DT and non-DT groups underscores a possible role of TNFR2 in DTs subtypes among AD patients undergoing withdrawal. The increase in TNFR2 levels following chronic and heavy alcohol consumption could be a compensatory response to prolonged inflammation and physiological imbalance. Further investigations are necessary to understand the mechanisms of TNFR2 in alcohol addiction more comprehensively.