Abstract
BACKGROUND: Preclinical and clinical research reveal associations between chronic alcohol use, increases in proinflammatory cytokines (interleukin [IL]-6, IL-8, tumor necrosis factor alpha [TNF-α]), and increases in alcohol consumption, alcohol craving, and negative mood. However, these findings remain largely correlational in clinical samples. Therefore, we conducted a preliminary inflammatory challenge using endotoxin in individuals with alcohol use disorder (AUD) to investigate the immune, behavioral, and brain responses to the inflammatory challenge. METHODS: Participants were randomly assigned to receive a bolus intravenous injection of either low-dose endotoxin (0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). Blood samples, sickness symptoms, physiology, mood, and alcohol craving were collected at baseline and hourly for 4 h postbaseline, with a neuroimaging scan occurring at 3 h postbaseline. Matched control data were used to validate the endotoxin challenge in comparison to the AUD sample. RESULTS: Endotoxin led to an acute blunted pro-inflammatory (i.e., TNF-α, IL-6, and IL-8) response in individuals with AUD compared to controls (all p's < 0.039). Endotoxin led to decreased cue-induced craving in both the behavioral human laboratory (p = 0.03) and neuroimaging (p's < 0.01) assays. Moreover, higher levels of endotoxin-induced IL-6 were most negatively associated with decreased self-reported craving following baseline (p < 0.05) in comparison with lower levels of endotoxin-induced IL-6. CONCLUSIONS: This preliminary study provides an acute experimental manipulation of inflammatory processes associated with AUD and suggests that the short-term effects of inflammation in AUD phenomenology are multifaceted and dose-dependent.