Acute Alcohol Intoxication Modulates Monocyte Subsets and Their Functions in a Time-Dependent Manner in Healthy Volunteers

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 Peripheral blood was withdrawn before and 2h (T2), 4h (T4), 6h (T6), 24h (T24), and 48h (T48) after starting the experiment and stained for CD14, CD16 and TLR4.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.

Differences in the subgingival microbial composition associated with alcohol intake: A systematic review

“…The increased proportions of specific periodontal pathogens caused by ethanol are possibly a result of the decreased commensals (i.e, Lactobacillales , Streptococcus and Rothia ) levels 12 , 44 and/or inflammation-related disturbances (which are expected to act on periodontal pocketing) associated with the immune subversion on the gingival crevicular fluid, ultimately impairing the host-microbial balance. 45 Previous studies also reported impaired neutrophil function 46 and reduced monocyte production of cytokines 47 following alcohol abuse, factors that contribute to increased bacterial proliferation and penetration. This complex interplay sheds light that the association of alcohol intake and periodontitis is driven by a shift in the subgingival microbial composition of those exposed.…”

Adolescent intermittent ethanol (AIE) produces lasting, sex-specific changes in rat body fat independent of changes in white blood cell composition

“…As CBC lacks the capacity to detect functional shifts in lymphocyte or monocyte subpopulations, future studies utilizing flow cytometry would allow for more extensive characterization of AIE-induced alterations of leukocyte immunoreactivity independent of total number changes. Indeed, much of the existing work examining alcohol effects on blood cells has shown effects on monocyte phenotype ( Janicova et al, 2021 ) or has investigated changes in human subjects with a history of AUD. These studies, while very informative, are often complicated by the poor diet ( Cummings et al, 2020 ), sedentary behavior, and other high-risk behaviors engaged by individuals with AUD, suggesting that adolescent alcohol exposure alone may not be the driving cause for many of the hematological complications associated with heavy alcohol use.…”

“…In humans, heavy alcohol consumption patterns are associated with abnormalities in RBC morphology, reduced platelet levels, and reduced WBC levels ( Ballard, 1997 ). While acute alcohol intoxication has been shown to alter monocyte populations, ultimately resulting in a decreased immune response to LPS challenge ( Mandrekar et al, 2009 ; Janicova et al, 2021 ), chronic alcohol exposure sensitizes monocytes to LPS ( Mandrekar et al, 2009 ). Chronic alcohol consumption also changes lymphocyte function, reducing both B ( Sacanella et al, 1998 ) and T cell ( Percival and Sims, 2000 ) levels as well as altering their activation (see Pasala et al, 2015 for relevant review).…”

The Alcohol Harm Paradox in Periodontitis

“…Such evidence should guide resource Schematic to interventions on alcohol consumption for those disadvantaged. Although there is no clear evidence suggesting a dysbiotic subgingival microbial profile in those exposed (Oliveira et al 2023), the relationship between alcohol intake and periodontitis seems to be explained by immune subversion on the gingival crevicular fluid due to impaired proinflammatory cytokine release (Janicova et al 2021) and decreased alveolar bone quality (Frazão et al 2020). Those of lower SEP are suggested to be more vulnerable to such a relationship due to the accumulation of adverse exposures that synergistically increase the likelihood of both alcohol harm and periodontitis and/or due to exposure to poor-quality beverages and binge drinking that increases the probability of periodontitis, even when the volume of consumption is the same of those of higher SEP. From a biological point of view, such a scenario may be explained as a result of the allostatic load—the “wear and tear” on the body associated with immune responses to chronic stress—on those of lower SEP.…”