Young alcohol binge drinkers have elevated blood endotoxin, peripheral inflammation and low cortisol levels: neuropsychological correlations in women

Abstract

Alcohol binge drinking is a pattern of heavy alcohol consumption that is increasingly practiced by adolescents and young adults. Evidence indicates that alcohol binges induce peripheral inflammation and an exacerbated neuroimmune response that may participate in alcohol-induced cognitive/behavioral dysfunctions. Here, we recruited 20-year-old male and female university students who were identified as binge drinkers for at least 2 years. Compared with controls, young alcohol binge drinkers had elevated levels of blood endotoxin and upregulated markers of the toll-like receptor 4/NF-κB inflammatory pathway in peripheral blood mononuclear cells, together with pro-inflammatory cytokine/chemokine release, oxidative stress and lipid peroxidation. These changes positively correlate with the estimated blood alcohol levels achieved during alcohol binge intoxication and negatively correlate with the time elapsed from the last alcohol consumption. The immune/inflammatory changes were more prominent in female drinkers, who showed elevated levels of alcohol danger-associated molecules, such as high mobility group box 1, indicating that there are sex-related differences in the peripheral inflammatory response to alcohol. In contrast, cortisol levels were decreased in alcohol binge drinkers. Finally, higher levels of inflammatory markers, mainly monocyte chemoattractant protein-1, as well as LPS, high mobility group box 1, toll-like receptor 4, IL-6 and ciclooxygenase-2, correlated with worse scores on episodic memory and executive functioning tasks in female binge drinkers but not in male binge drinkers. These results emphasize possible risky consequences of alcohol use in binge episodes during young adulthood and call attention to sex-related differences in the alcohol-induced immune/inflammatory and neurocognitive responses.

Alcohol binge disrupts the rat intestinal barrier: the partial protective role of oleoylethanolamide

“…Increased OEA release in the small intestine was observed in response to alcohol in vivo (Bilbao et al ., ) and to inflammation in vitro (Karwad et al ., ), suggesting a local role of OEA in regulating alcohol responses and intestinal permeability respectively. The idea that inflammation may trigger the release of OEA has been also proposed in our previous studies, in which we observed exacerbated inflammatory responses and increased plasma OEA levels in human alcohol binge drinkers (Orio et al ., ; Antón et al, ). Alcohol also induced neuroinflammation and OEA release in the frontal cortex of laboratory animals (Bilbao et al ., ; Antón et al ., ).…”

“…A single alcohol binge has been shown to induce a transient increase in serum endotoxin and bacterial DNA levels in healthy subjects (Bala et al ., ). We have recently reported that repeated alcohol binges increase plasma LPS in rats (Antón et al ., ) and humans (Orio et al ., ) and promote an inflammatory response that may have consequences for neurocognitive performance. However, the effects of binge drinking on intestinal barrier integrity, bacterial translocation and the mechanisms involved in gut barrier dysfunction have yet to be comprehensively investigated.…”

“…In previous studies, we demonstrated that pharmacological pretreatment with oleoylethanolamide (OEA), a lipid mediator part of the acylethanolamide family, during the alcohol binge episodes has potent anti‐inflammatory, antioxidant and neuroprotective properties against the effects of alcohol and partially reduced alcohol binge‐induced increases in plasma LPS levels in rats (Antón et al ., ). In humans, we observed that regular alcohol binge drinkers show elevated plasma levels of LPS and inflammatory markers (Orio et al ., ) and increased plasma levels of OEA and similar biolipids (Antón et al ., ), suggesting a homeostatic role for this biolipid in regulating alcohol responses (Bilbao et al ., ). The main hypothesis that we tested in this study was whether the anti‐inflammatory actions of OEA may have a local action in the gut, regulating inflammation and barrier permeability.…”

Binge drinking in adolescence predicts an atypical cortisol stress response in young adulthood

“…Emerging cross-sectional literature documents associations between alcohol use outside of the experimental context and alterations to the expected cortisol stress response profile (e.g., Orio et al, 2017). Only one study to our knowledge has prospectively examined alcohol use and biological stress system functioning.…”

“…With one exception (e.g., Jones et al, 2013), cross-sectional studies with humans have shown an attenuation of the neuroendocrine response to stress (i.e., a decrease in levels across an acute stressor) among adults who report binge drinking or other forms of heavy alcohol use (Lovallo et al, 2000;Orio et al, 2017). Atypical patterns of cortisol reactivity, such as a blunted response, have been associated with a wide range of physical and mental health problems (for a review, see Phillips et al, 2013).…”