Alcohol-dependent pulmonary inflammation: A role for HMGB-1
Open accessAbstract
Previous studies have demonstrated that acute alcohol intoxication significantly impairs lung immune responses, which can lead to the tissue being undefended from microbial infection and resulting disease. Data suggest that acute intoxication presents an axis where simultaneously suppressing early pro-inflammatory cytokines while inducing anti-inflammatory signals contributes to alcohol-dependent immune suppression in the lung, and thus undeterred microbial replication. Interestingly, alcoholics and those with alcohol use disorder present with increased pneumonia and acute respiratory diseases (ARDs), suggesting a more active priming of inflammatory responses in the lungs. There is current research evaluating the acute effects of binge ethanol consumption on adolescents, which is of grave concern, though long-term effects of adolescent ethanol binge exposure are less studied. We hypothesize that adolescent binge drinking may prime the individual to severe pulmonary distress, when later challenged by a microbial pathogen. Herein, we evaluate a model of adolescent intermittent ethanol (AIE) exposure to investigate pulmonary pathology after microbial challenge. Ethanol was administered to adolescent mice using a binge exposure schedule, and mice were then rested to early adulthood. These mice were then challenged with a sub-lethal intranasal inoculation of Klebsiella pneumoniae and evaluated for severity of disease. We find that AIE exposure initially activates inflammatory mediators within the lung, which resolves over time. However, when challenged with a microbial pathogen after this resolution period, these animals present with more severity of inflammation, pulmonary tissue damage, and mortality when challenged with a pulmonary microbial infection. Interestingly, our data suggest a role for alcohol-dependent release of the protein HMGB-1 from host cells, for both morbidity and mortality in our model of microbial-dependent pulmonary inflammation.
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Ethanol exposure can increase soluble RAGE expression in bronchoalveolar lavage fluid together with RAGE ligand HMGB1 in inflammatory lung.
“In addition to adduct formation, ethanol exposure can increase soluble RAGE expression in bronchoalveolar lavage fluid together with RAGE ligand (HMGB1) in the inflammatory lung239,240.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [240]
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- Authors
- Harris, B., Mcalister, A., Willoughby, T., & Sivaraman, V.
- Affiliations
- North Carolina Central University (US)
- Corresponding author
- Sivaraman, Vijay
- ORCID
- Sivaraman, Vijay
- Venue
- Alcohol
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 80
- Pages
- 45-52
- ISSN
- 0741-8329 (ISSN-L)
- PMC
- PMC6443509
- OpenAlex
- W2894656749
- Cited by
- 22
- References
- 37
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 7 · 2020: 2 · 2019: 1
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcohol (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of North Carolina
- North Carolina Central University
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- alcoholism, HMGB1, lung inflammation, adolescent intermittent ethanol exposure, binge drinking, Klebsiella pneumoniae, pulmonary infection, inflammatory cytokines, lung injury
- MeSH terms
- Ethanol, Animals, Disease Models, Animal, Female, Klebsiella Infections, Klebsiella pneumoniae, Male, Mice, Inbred C57BL, Cytokines, Pneumonia, Bacterial, HMGB1 Protein, Mice, Binge Drinking
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