Inflammatory endotoxin challenge in individuals with alcohol use disorder and controls

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.