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Alcohol Use As a Risk Factor in Infections and Healing

View Article: PubMed Central

ABSTRACT

Physicians have recognized for more than a century that alcohol use is associated with infections and that alcoholics are especially at risk for pneumonia. Clear evidence now indicates that alcohol has a systemic effect on every organ. This review first presents a clinical case to describe a patient with immunity issues complicated by alcohol use—a setting familiar to many clinicians. This is followed by a description of the molecular mechanisms that explain the secondary immune deficiency produced by alcohol in the host, focusing mostly on the gut and lower respiratory mucosal immunity. The goal of this review is to increase awareness of the new mechanisms being investigated to understand how alcohol affects the human immune system and the development of new strategies to attenuate adverse outcomes in the affected population.

No MeSH data available.


Related in: MedlinePlus

Alcohol use increases intestinal permeability and endotoxin levels. The mechanisms include increases in microRNA miR-212 levels, which decrease gene expression within the zonula occludens, resulting in increases to miR-155 that produce intestinal inflammation. Alcohol induces expression of the enzyme CYP2E1, increasing reactive oxygen species, which damage tissue through increases in oxidative stress. Alcohol also increases the expression of circadian clock genes that alter intestinal permeability.
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f1-arcr-37-2-177: Alcohol use increases intestinal permeability and endotoxin levels. The mechanisms include increases in microRNA miR-212 levels, which decrease gene expression within the zonula occludens, resulting in increases to miR-155 that produce intestinal inflammation. Alcohol induces expression of the enzyme CYP2E1, increasing reactive oxygen species, which damage tissue through increases in oxidative stress. Alcohol also increases the expression of circadian clock genes that alter intestinal permeability.

Mentions: The exact mechanisms underlying alcohol’s role in increasing gut permeability and/or transient endotoxemia are not clearly elucidated, but recent studies have suggested some possible causes (see figure). Cytochrome P4502E1 is an enzyme present in the liver and is involved in the metabolism and oxidation of alcohol, fatty acids, and foreign compounds (Cederbaum 2010). CYP2E1 is the most highly expressed isoform of the CYP450 cytochrome enzymes and is highly expressed not only in the liver but also in the small intestine and colon. In addition, an acute model of alcohol binge intoxication in mice shows that alcohol can induce the expression of intestinal CYP2E1 and that this induction is correlated with higher endotoxemia and translocation of liver bacteria. These outcome measures were substantially reduced, however, in Cyp2e1− mice (genetically modified mouse in which Cyp2e1 gene is inactive) compared with wild-type control mice, suggesting that CYP2E1 is essential for development of gut leakiness. The deleterious effects of alcohol-induced CYP2E1 were ameliorated with treatment with the antioxidant N-acetylcysteine (Abdelmegeed et al. 2013).


Alcohol Use As a Risk Factor in Infections and Healing
Alcohol use increases intestinal permeability and endotoxin levels. The mechanisms include increases in microRNA miR-212 levels, which decrease gene expression within the zonula occludens, resulting in increases to miR-155 that produce intestinal inflammation. Alcohol induces expression of the enzyme CYP2E1, increasing reactive oxygen species, which damage tissue through increases in oxidative stress. Alcohol also increases the expression of circadian clock genes that alter intestinal permeability.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590615&req=5

f1-arcr-37-2-177: Alcohol use increases intestinal permeability and endotoxin levels. The mechanisms include increases in microRNA miR-212 levels, which decrease gene expression within the zonula occludens, resulting in increases to miR-155 that produce intestinal inflammation. Alcohol induces expression of the enzyme CYP2E1, increasing reactive oxygen species, which damage tissue through increases in oxidative stress. Alcohol also increases the expression of circadian clock genes that alter intestinal permeability.
Mentions: The exact mechanisms underlying alcohol’s role in increasing gut permeability and/or transient endotoxemia are not clearly elucidated, but recent studies have suggested some possible causes (see figure). Cytochrome P4502E1 is an enzyme present in the liver and is involved in the metabolism and oxidation of alcohol, fatty acids, and foreign compounds (Cederbaum 2010). CYP2E1 is the most highly expressed isoform of the CYP450 cytochrome enzymes and is highly expressed not only in the liver but also in the small intestine and colon. In addition, an acute model of alcohol binge intoxication in mice shows that alcohol can induce the expression of intestinal CYP2E1 and that this induction is correlated with higher endotoxemia and translocation of liver bacteria. These outcome measures were substantially reduced, however, in Cyp2e1− mice (genetically modified mouse in which Cyp2e1 gene is inactive) compared with wild-type control mice, suggesting that CYP2E1 is essential for development of gut leakiness. The deleterious effects of alcohol-induced CYP2E1 were ameliorated with treatment with the antioxidant N-acetylcysteine (Abdelmegeed et al. 2013).

View Article: PubMed Central

ABSTRACT

Physicians have recognized for more than a century that alcohol use is associated with infections and that alcoholics are especially at risk for pneumonia. Clear evidence now indicates that alcohol has a systemic effect on every organ. This review first presents a clinical case to describe a patient with immunity issues complicated by alcohol use—a setting familiar to many clinicians. This is followed by a description of the molecular mechanisms that explain the secondary immune deficiency produced by alcohol in the host, focusing mostly on the gut and lower respiratory mucosal immunity. The goal of this review is to increase awareness of the new mechanisms being investigated to understand how alcohol affects the human immune system and the development of new strategies to attenuate adverse outcomes in the affected population.

No MeSH data available.


Related in: MedlinePlus