ArticleAlcohol and alcoholism (Oxford, Oxfordshire)2018
Interactions between TLR4 methylation and alcohol consumption on subjective responses to an alcohol infusion.
Article in Alcohol and alcoholism (Oxford, Oxfordshire), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Central amygdala neuroimmune signaling in alcohol use disorder.Addiction neuroscience · 2025Article
- Non-coding RNA in alcohol use disorder by affecting synaptic plasticity.Experimental brain research · 2022Review
- Skeletal muscle satellite cell-derived mesenchymal stem cells ameliorate acute alcohol-induced liver injury.International journal of medical sciences · 2022Article
- Toll-Like Receptor 4: A Novel Target to Tackle Drug Addiction?Handbook of experimental pharmacology · 2022Article
- Stress and Alcohol Priming of Brain Toll-Like Receptor Signaling in Alcohol Use Disorder.Alcohol and alcoholism (Oxford, Oxfordshire) · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
aimsConverging evidence has implicated perturbed inflammatory signaling in alcohol use disorders (AUDs), and both animal and human studies suggest that alcohol-induced inflammatory signaling is mediated by Toll-Like Receptor 4 (TLR4). We previously demonstrated that TLR4 is hypermethylated in subjects with AUD compared to control individuals. Examining the relationship between TLR4 methylation and subjective alcohol responses could shed light on the role of TLR4 in promoting AUDs, thereby highlighting its potential as a treatment target. SHORT SUMMARY: Significant interactions were demonstrated between Toll-like Receptor 4 (TLR4) methylation and human alcohol consumption patterns, such that greater methylation was associated with decreased positive and negative self-reported arousal during an alcohol infusion among light-to-moderate drinkers, but increased self-reported positive arousal and physiological arousal (i.e. systolic blood pressure) among heavy drinkers.
methodsLatent growth models were used to examine the relationship between TLR4 methylation and subjective responses and physiological measures of arousal during an alcohol infusion across 222 drinkers.
resultsWe observed significant interactions of TLR4 methylation and alcohol use (drinks per week) on intercepts for self-report and physiological arousal measures. Specifically, light-to-moderate drinkers had positive associations between methylation and stimulation and tension (r's = 0.21-0.24), and heavy drinkers had negative associations (r's = -0.15 to -0.21). There were also significant interaction effects on changes in tension (β = 0.31, P < 0.01), systolic blood pressure (β = 0.74, P < 0.01) and marginal effects on stimulation (β = 0.15, P = 0.07) during the infusion, such that methylation was associated with decreased arousal among light-to-moderate drinkers (r's = -0.12 to -0.25) but stable or increased arousal among heavy drinkers (r's = 0.05-0.19).
conclusionsFindings suggest that the relationship between TLR4 methylation and subjective and physiological arousal during acute alcohol intoxication depends upon on self-reported alcohol use. These data demonstrate the influence of TLR4 on subjective responses to alcohol, thereby supporting the need for further research on its potential as a pharmacological treatment target.
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