Reduced phagocytosis, ROS production and enhanced apoptosis of leukocytes upon alcohol drinking in healthy volunteers

Abstract

Background Alcohol drinking is associated with a serious risk of developing health problems as well as with a large number of traumatic injuries. Although chronic alcohol misuse is known to contribute to severe inflammatory complications, the effects of an acute alcohol misuse are still unclear. Here, the impact of acute alcohol drinking on leukocyte counts and their cellular functions were studied. Methods Twenty-two healthy volunteers (12 female, 10 male) received a predefined amount of a whiskey-cola mixed drink (40% v/v), at intervals of 20 min, over 4 h to achieve a blood alcohol concentration of 1‰. Blood samples were taken before drinking T0, 2 h (T2), 4 h (T4), 6 h (T6), 24 h (T24) and 48 h (T48) after starting drinking alcohol. Leukocytes, monocytes and granulocyte counts and their functions regarding the production of reactive oxidative species (ROS), phagocytosis and apoptosis were analyzed by flow cytometry. Results Total leukocyte counts significantly increased at T2 and T4, while granulocyte and monocyte counts decreased at T4 and T6 vs. T0. Monocytes increased significantly at T24 and T48 vs. T0. While the total number of ROS-producing leukocytes and notably granulocytes significantly increased, in parallel, the intracellular ROS intensity decreased at T2 and T6. The numbers of ROS-positive monocytes have shown a delayed modulation of ROS, with a significant reduction in the total number of ROS-producing cells at T48 and a significantly reduced intracellular ROS-intensity at T24. Phagocyting capacity of leukocytes significantly decreased at T4 and T6. In general leukocytes, and notably granulocytes demonstrated significantly increased early (T2), while monocyte exerted significantly increased late apoptosis (T24 and T48). Conclusions Alcohol drinking immediately impacts leukocyte functions, while the impact on monocytes occurs at even later time points. Thus, even in young healthy subjects, alcohol drinking induces immunological changes that are associated with diminished functions of innate immune cells that persist for days.

Usnic Acid and Usnea barbata (L.) F.H. Wigg. Dry Extracts Promote Apoptosis and DNA Damage in Human Blood Cells through Enhancing ROS Levels

“…In addition, low ROS concentration can promote cell proliferation, whereas excessive ROS levels cause DNA oxidative damage, consequently inducing cell death [ 105 ]. ROS levels are implicated in all blood cell lines death: platelets [ 106 , 107 ], RBCs [ 108 , 109 ], and WBCs [ 110 , 111 ].…”

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

“…However, the immunosuppressive effect of alcohol seems to affect the functionality of individual monocyte subsets without changing their ratios at T48. In line with this, less monocytes are positive for reactive oxygen species at 48 hours after binge drinking, suggesting lower antimicrobial competence (25). Acute alcohol intoxication-related decrease in TLR4 response, so-called TLR4 tolerance, is induced by B-cell lymphoma 3-encoded protein (Bcl-3) that negatively regulates TNF-a transcription (34).…”

“…Regarding the delayed increase of the relative nonclassical monocyte fraction, it seems, that alcohol intoxication converts the intermediate into non-classical monocytes and thereby, switch their pro-inflammatory character into an immunosuppressive cell type. Under the same experimental settings, it has been shown that absolute leukocyte numbers significantly increase two and four hours after starting alcohol drinking, suggesting an early mobilization of immune system (25). The percentage of granulocytes out of all leukocytes decreases significantly at four and six hours, whereas the monocyte percentage decreases first significantly at six hours with subsequent significant elevation at 24 and 48 hours postdrinking (25).…”

“…Under the same experimental settings, it has been shown that absolute leukocyte numbers significantly increase two and four hours after starting alcohol drinking, suggesting an early mobilization of immune system (25). The percentage of granulocytes out of all leukocytes decreases significantly at four and six hours, whereas the monocyte percentage decreases first significantly at six hours with subsequent significant elevation at 24 and 48 hours postdrinking (25). The current literature describes changes in leukocyte subpopulations almost exclusively in chronic alcohol abuse, although these changes are not less relevant in acute setting of alcohol drinking.…”

“…Combining the absolute cell numbers of leukocytes per microliter (25) with the relative fractions of monocytes and their subsets, we converted the percentages of monocyte subsets into absolute cell numbers. These are summarized in Supplementary Table 1.…”