Acute immunomodulatory effects of binge alcohol ingestion

Abstract

BACKGROUND Blood alcohol is present in a third of trauma patients and has been associated with organ dysfunction. In both human studies and in animal models, it is clear that alcohol intoxication exerts immunomodulatory effects several hours to days after exposure, when blood alcohol is no longer detectable. The early immunomodulatory effects of alcohol while blood alcohol is still elevated are not well understood. METHODS Human volunteers achieved binge alcohol intoxication after high-dose alcohol consumption. Blood was collected for analysis prior to alcohol ingestion, and 20 min, 2 h, and 5 h after alcohol ingestion. Flow cytometry was performed on isolated peripheral blood mononuclear cells, and cytokine generation in whole blood was measured by enzyme-linked immunosorbent assay (ELISA) after 24-h stimulation with lipopolysaccharide (LPS) and phytohemagglutinin-M (PHA) stimulation. RESULTS An early pro-inflammatory state was evident at 20 min when blood alcohol levels were ~130 mg/dL, which was characterized by an increase in total circulating leukocytes, monocytes, and natural killer cells. During this time, a transient increase in LPS-induced tumor necrosis factor (TNF)-α levels and enhanced LPS sensitivity occurred. At 2 and 5 h post-alcohol binge, an anti-inflammatory state was shown with reduced numbers of circulating monocytes and natural killer cells, attenuated LPS-induced interleukin (IL)-1β levels, and a trend toward increased interleukin (IL)-10 levels. CONCLUSIONS A single episode of binge alcohol intoxication exerted effects on the immune system that caused an early and transient pro-inflammatory state followed by an anti-inflammatory state.

Opposing effects of alcohol on the immune system

“…However, similarly to the in vitro studies described above, at 2 and 5 hours post-binge the numbers of circulating monocytes were reduced and levels of antiinflammatory IL-10 levels were increased (Afshar, Richards et al 2014). …”

Binge Drinking in Young Adulthood: The Influence of Age at First Intercourse and Rate of Sex Partner Accumulation

“…From a public policy perspective, understanding the factors that put individuals at risk for engaging in frequent binge drinking is crucial, as studies show that frequent binge drinkers experience worse health-related quality of life (Okoro et al, 2004), sleep problems (Popovici & French, 2013), and suppressed immune functioning (Afshar et al, 2015). Furthermore, understanding the prevalence of binge drinking among young adults in their mid-twenties and early thirties may be particularly important, as it may have implications as they transition into new social environments and social roles.…”

Ethanol and Other Short-Chain Alcohols Inhibit NLRP3 Inflammasome Activation through Protein Tyrosine Phosphatase Stimulation

“…Binge alcohol consumption suppresses host innate immune defense, while chronic alcohol consumption suppresses innate and adaptive immune systems, yet activates chronic inflammation (27). Ethanol is a known inhibitor of NF-κB activation and its consumption is associated with decreased circulating levels of TNF and IL-1β (28, 29). Recently, ethanol, but not its metabolite acetaldehyde, was found to also be capable of inhibiting step 2 for the NLRP3 and AIM2 inflammasomes (22).…”

“…Furthermore, the effects of ethanol exposure can be cell type specific. Ethanol has been shown to induce inflammation and inflammatory cytokine release in the brain (via astrocytes, neurons, and microglia) and liver (via Kupffer cells), alongside its paradoxical tendency to induce immune suppression of leukocytes in the rest of the body (22, 28, 29, 36–40). …”