Abstract
BackgroundExcessive alcohol intake is associated with adverse immune response-related effects, however, acute and chronic abuse differently modulate monocyte activation. In this study, we have evaluated the phenotypic and functional changes of monocytes in acutely intoxicated healthy volunteers (HV).MethodsTwenty-two HV consumed individually adjusted amounts of alcoholic beverages until reaching a blood alcohol level of 1‰ after 4h (T4). Peripheral blood was withdrawn before and 2h (T2), 4h (T4), 6h (T6), 24h (T24), and 48h (T48) after starting the experiment and stained for CD14, CD16 and TLR4. CD14brightCD16-, CD14brightCD16+ and CD14dimCD16+ monocyte subsets and their TLR4 expression were analyzed by flow cytometry. Inflammasome activation via caspase-1 in CD14+ monocytes was measured upon an ex vivo in vitro LPS stimulation. Systemic IL-1β and adhesion capacity of isolated CD14+ monocytes upon LPS stimulation were evaluated.ResultsThe percentage of CD14+ monocyte did not change following alcohol intoxication, whereas CD14brightCD16- monocyte subset significantly increased at T2 and T24, CD14brightCD16+ at T2, T4 and T6 and CD14dimCD16+ at T4 and T6. The relative fraction of TLR4 expressing CD14+ monocytes as well as the density of TLR4 surface presentation increased at T2 and decreased at T48 significantly. TLR4+CD14+ monocytes were significantly enhanced in all subsets at T2. TLR4 expression significantly decreased in CD14brightCD16- at T48, in CD14brightCD16+ at T24 and T48, increased in CD14dimCD16+ at T2. IL-1β release upon LPS stimulation decreased at T48, correlating with TLR4 receptor expression. Alcohol downregulated inflammasome activation following ex vivo in vitro stimulation with LPS between T2 and T48 vs. T0. The adhesion capacity of CD14+ monocytes decreased from T2 with significance at T4, T6 and T48. Following LPS administration, a significant reduction of adhesion was observed at T4 and T6.ConclusionsAlcohol intoxication immediately redistributes monocyte subsets toward the pro-inflammatory phenotype with their subsequent differentiation into the anti-inflammatory phenotype. This is paralleled by a significant functional depression, suggesting an alcohol-induced time-dependent hyporesponsiveness of monocytes to pathogenic triggers.
Highlights
Alcohol is one of the oldest and nowadays one of the most common addictive substances worldwide [1]
Considering that phenotypic and functional alterations of monocytes are substantially involved in the initiation and subsequent resolution of inflammation, we evaluated the phenotypic shift of monocytes following episodic excessive alcohol intake in healthy volunteers (HV)
Since it is known that alcohol misuse has modulating effects on the immune system, we investigated the distribution of different monocytes subsets in healthy volunteers following excessive acute alcohol intake
Summary
Alcohol is one of the oldest and nowadays one of the most common addictive substances worldwide [1]. Following binge drinking, defined as an episodic excessive alcohol intake and the most common form of alcohol abuse, the counts of circulating leukocytes, monocytes and natural killer cells as well as the release of tumor necrosis factor (TNF)-a after an ex vivo in vitro whole blood stimulation with lipopolysaccharide (LPS) increase in the first 20 minutes after drinking, suggesting an early pro-inflammatory response. Subsequent decline of monocytes, natural killer cells and interleukin (IL)-1b, IL-6 and monocyte chemoattractant protein (MCP)-1 levels in circulation and the elevation of systemic IL-10 level suggest an antiinflammatory state in the later course [7, 9, 12] In line with this data, leukocytes and IL-6 decrease in circulation was observed in severely injured patients with excessive alcohol intoxication [10]. We have evaluated the phenotypic and functional changes of monocytes in acutely intoxicated healthy volunteers (HV)
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