Dose-dependent effects of chronic alcohol drinking on peripheral immune responses

Sureshchandra, Suhas; Raus, Anthony M.; Jankeel, Allen; Ligh, Brian Jin Kee; Walter, Nicole A.R.; Newman, Natali; Grant, Kathleen A.; Messaoudi, Ilhem

doi:10.1038/s41598-019-44302-3

Cited by 53 publications

(91 citation statements)

References 72 publications

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“…Chronic ethanol abuse almost doubles the risk of developing acute respiratory distress syndrome [ 59 ]. The association between bacterial and viral lung infections and ethanol dependence is supported by multiple pathophysiological mechanisms [ 60 , 59 , 61 ]:…”

Section: Alcohol Consumption Immune System and Covid-19mentioning

confidence: 99%

COVID-19 pandemic and alcohol consumption: Impacts and interconnections

et al. 2021

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Section: Alcohol Consumption Immune System and Covid-19mentioning

confidence: 99%

COVID-19 pandemic and alcohol consumption: Impacts and interconnections

et al. 2021

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“…Moreover, our DEG analysis, suggested two genes, Elovl6 and Sult2a3, changed by exposure of alcohol in both diets (diet-independent) that can potentially be used to design alcohol specific, diet independent, drug targeting but also potential diet independent biomarkers of alcohol toxicity. www.nature.com/scientificreports www.nature.com/scientificreports/ Previous published work showed that alcohol effects on immune system are dependent of the duration and dose of alcohol exposure as well as gender and age of mice, so our present comparative work between these two most common murine chronic models used to study the effect of alcohol has some limitations 19,54,55 .…”

Section: Discussionmentioning

confidence: 99%

“…Secondly, chronic alcohol drinking increases inflammatory transcriptomic profile following LPS stimulation in peripheral blood mononuclear cells in dose dependent manner 54 . A confounding factor in our study is that the amount of alcohol per day consumed in LD model was higher compared with MC model in spite of more extended time of alcohol exposure in MC mice.…”

Section: Discussionmentioning

confidence: 99%

Restricted immunological and cellular pathways are shared by murine models of chronic alcohol consumption

Vogle

Qian

Zhu

et al. 2020

Sci Rep

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Murine models of chronic alcohol consumption are frequently used to investigate alcoholic liver injury and define new therapeutic targets. Lieber-DeCarli diet (LD) and Meadows-Cook diet (MC) are the most accepted models of chronic alcohol consumption. It is unclear how similar these models are at the cellular, immunologic, and transcriptome levels. We investigated the common and specific pathways of LD and MC models. Livers from LD and MC mice were subjected to histologic changes, hepatic leukocyte population, hepatic transcripts level related to leukocyte recruitment, and hepatic RNA-seq analysis. Cross-species comparison was performed using the alcoholic liver disease (ALD) transcriptomic public dataset. Despite LD mice have increased liver injury and steatosis by alcohol exposure, the number of CD45 + cells were reduced. Opposite, MC mice have an increased number of monocytes/liver by alcohol. The pattern of chemokine gradient, adhesion molecules, and cytokine transcripts is highly specific for each model, not shared with advanced human alcoholic liver disease. Moreover, hepatic RNA-seq revealed a limited and restricted number of shared genes differentially changed by alcohol exposure in these 2 models. Thus, mechanisms involved in alcohol tissue injury are model-dependent at multiple levels and raise the consideration of significant pathophysiological diversity of human alcoholic liver injury. Murine models are frequently used to investigate new pathophysiological pathways of human diseases and many new treatment trials for alcoholic liver disease (ALD) are based on preclinical testing provided by murine models. ALD in humans is the result of a complex interaction between the alcoholic effects on gut microbiota, intestinal cells, immune system, and the hepatic microenvironment 1,2. Based on an extensive body of literature, alcohol increases the intestinal permeability and subsequent systemic translocation of bacterial products, e.g. LPS 1,3,4. Stimulation of Toll-like receptors (TLR) by bacterial products results in immune cell activation related to hepatic alcohol metabolic process that has a deleterious effect on the liver, resulting in histological features of ALD: steatosis, innate immune infiltrate with predominance of neutrophils and monocytes, and histological signs of hepatocyte dysfunction (Mallory hyaline formation, ballooning hepatocyte) 3,5-7. ALD includes a spectrum of histological and clinical entities: steatosis, steatohepatitis, and alcoholic hepatitis 8,9. In time, chronic liver injury with a dysregulated innate immune response results in alcohol-induced progressive hepatic fibrogenesis, liver cirrhosis and end-stage liver disease 10. Based on this classical paradigm, few trials have been attempted to control an exacerbated innate immune response or to improve hepatocyte function. Besides steroids that may be beneficial for only subsets of patients with alcoholic hepatitis 11 , no other treatments have proven consistent survival benefit 12. Moreover, treatment of anti-TNFα in alcoholic hepati...

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“…Interestingly, the pro-inflammatory impact of drinking was significant only with chronic heavy alcohol drinking. These transcriptional changes are being claimed to be partially explained by alterations in microRNA profiles (Sureshchandra et al 2019a).…”

Section: Cancermentioning

confidence: 99%

Ethanol and its metabolites: update on toxicity, benefits, and focus on immunomodulatory effects

Daré

Lagente

Gicquel

2019

Drug Metabolism Reviews

110

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This article summarizes recent experimental and epidemiological data on the toxic and beneficial effects of ethanol and its metabolites (acetaldehyde), and focuses on their immunomodulatory effects. The section dealing with the toxic effects of alcohol focuses on its chronic toxicity (liver disorders, carcinogenic effects, cardiovascular disorders, neuropsychic disorders, addiction and withdrawal syndrome, hematologic disorders, reprotoxicity, osteoporosis) although acute toxicity is considered. The role of oxidative metabolism of ethanol by alcohol dehydrogenase, cytochrome P450 2E1, and aldehyde dehydrogenase, as well as the impact of genetic polymorphism in its physiopathology are also highlighted. The section dealing with the beneficial effects of low to moderate alcohol consumption (on cardiovascular system, diabetes, the nervous system and sensory organs, autoimmune diseases, and rheumatology) highlights the importance of anti-inflammatory and immunomodulatory effects in these observations. This knowledge, enriched by a focus on the immunomodulatory effects of ethanol and its metabolites, in particular on the NLRP3 inflammasome pathway, might facilitate the development of treatments that can reduce ethanol's harmful effects or accentuate its beneficial effects.

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Dose-dependent effects of chronic alcohol drinking on peripheral immune responses

Cited by 53 publications

References 72 publications

COVID-19 pandemic and alcohol consumption: Impacts and interconnections

COVID-19 pandemic and alcohol consumption: Impacts and interconnections

Restricted immunological and cellular pathways are shared by murine models of chronic alcohol consumption

Ethanol and its metabolites: update on toxicity, benefits, and focus on immunomodulatory effects

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