Alcohol use disorder and circulating cytokines: A systematic review and meta-analysis

There has been emerging interest in the role of the immune system in the pathophysiology of alcohol use disorder (AUD) given alcohol consumption stimulates immune cells to secrete peripheral pro- and anti-inflammatory cytokines. We conducted a systematic review and meta-analysis to determine whether an abnormal inflammatory cytokine profile exists in AUD patients compared to controls and whether cytokine levels were correlated with behavioural and psychiatric variables. Using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a comprehensive search of electronic databases (MEDLINE, EMBASE, Web of Science Core Collection and the Cochrane Library) was conducted, for AUD-related terms in combination with cytokine-related terms. Patients had to meet established criteria for AUD and be compared with healthy controls. A critical appraisal was completed using the Newcastle-Ottawa Scale. Twenty-four papers met the inclusionary criteria with 46 serum or plasma cytokines measured without immune stimulation whereby 17 studies had sufficient data for inclusion in the meta-analysis. Collectively, AUD patients had greater cytokine concentrations than control patients g = 0.85 [ 95% CI 0.42, 1.29]. Differences in cytokine concentrations between AUD patients and controls varied within-study by stage of illness (R-(2)(2) = 19.56%). The greatest differences were reported when AUD patients were engaging in active drinking g = 0.96 [0.49, 1.43] or were in alcohol withdrawal g = 1.25 [0.71, 1.80]. Baseline findings were moderated within and between studies by cytokine identity R-(2)(2) = 51.10%; R-(3)(2) = 44.89%. Cytokine concentrations were not significantly correlated with self-reported craving for alcohol, but were with alcohol consumption r = 0.22 [-0.05, 0.46]. The relationship between cytokine concentration and consumption was moderated by cytokine identity (R( 2)2 = 100.00%; R-(3)(2) = 100.00%), and sample age (R-(2)(2) = 0.00%; R-(3)(2) = 95.76%). There is sufficient evidence to support the presence of an abnormal circulating cytokine profile in AUD which may vary with respect to the different stages of AUD illness.