Peripheral Immune System Adaptations and Motivation for Alcohol in Non-Dependent Problem Drinkers

Abstract

Aims Increasing evidence suggests that levels of pro-inflammatory and anti-inflammatory cytokines are dysfunctional in alcohol dependence. Moreover, some initial findings demonstrate that these adaptations in peripheral inflammation may contribute to motivation for alcohol and problem drinking via possible direct effects or the indirect effects of stress responsivity. Importantly, the role of pro-inflammatory and anti-inflammatory cytokines in the progression from healthy to problem drinking is not well understood. The aim of the current study was to assess whether alcohol-related peripheral immune system changes affect stress and alcohol cue-induced craving and anxiety and behavioral alcohol motivation and intake in the laboratory among problem drinkers compared with socially drinking controls. Methods Twenty-six problem drinkers and 38 moderate, social drinkers participated in a laboratory challenge procedure during which they were exposed to 3 personalized 5-minute imagery conditions (stress (S), relaxing (R) and alcohol cue (C), followed by the “alcohol taste test” (ATT) as a measure of implicit alcohol motivation and intake, presented across 3 consecutive days, one per day in a randomized and counterbalanced order. Measures of Tumor Necrosis Factor alpha (TNFα), Interleukin-6 (IL-6), Interleukin-1 receptor antagonist (IL-1ra), alcohol craving and anxiety were assessed at baseline, immediately following imagery exposure and at discreet beer cue presentation in the ATT. Results Compared with moderate drinkers, problem drinkers demonstrated tonic attenuation of IL-6 and IL-1ra. In problem drinkers, these changes also accompanied elevated levels of stress and cue-induced alcohol craving, anxiety, and were predictive of provoked alcohol craving, behavioral alcohol motivation and intake and severity of problem drinking. Conclusions Current findings indicate that selective immunosuppression in problem drinkers may play a key role in motivation for alcohol intake.

Peripheral immune system suppression in early abstinent alcohol-dependent individuals: Links to stress and cue-related craving

“…Findings from our recent study of problem drinkers have additionally shown immune-suppression to predict craving, severity of problem use and alcohol consumption (Milivojevic in press). Marcos et al, (2008) also demonstrated a significant association between the −592C>A polymorphism of IL-10 and alcoholism, with an excess of allele A carriers being observed in alcohol dependent individuals (Crawley et al, 1999).…”

Stress vulnerability and alcohol use and consequences: From human laboratory studies to clinical outcomes

“…Twenty-six problem drinkers and 38 social drinkers (see Table 2) - participated in a laboratory challenge procedure during which they were exposed to 3 personalized 5-minute imagery conditions (stress, relaxing, and alcohol cue, described in Section I), followed by the “alcohol taste test” (ATT) as a measure of implicit alcohol motivation and intake, presented across 3 consecutive days, 1 per day in a randomized and counterbalanced order (Milivojevic et al , 2017). Participants were characterized as problem or social drinkers according to Alcohol Use Disorder Identification Test (AUDIT) scores (>8 problem drinker, <8 social drinker).…”

Craving, cortisol and behavioral alcohol motivation responses to stress and alcohol cue contexts and discrete cues in binge and non‐binge drinkers

“…1). Context on each day was induced using our well-validated personalized guided imagery laboratory procedures which individually calibrate personal stressful events and have been shown to reliably provoke stress-induced and cue-induced craving in those with and without substance use disorders (Fox et al 2005; Fox et al 2007; Sinha et al 2007; Chaplin et al 2008; Sinha et al 2009; Sinha 2009b; Seo et al 2011; Fox et al 2010; Sinha et al, 2011a; Seo et al 2013; Milivojevic et al 2017). Finally, subjective craving and cortisol responses were also assessed post-ATT to examine both context and alcohol intake effects on these responses.…”