Aliphatic alcohols in spirits inhibit phagocytosis by human monocytes

Abstract

A large volume of alcoholic beverages containing aliphatic alcohols is consumed worldwide. Previous studies have confirmed the presence of ethanol-induced immunosuppression in heavy drinkers, thereby increasing susceptibility to infectious diseases. However, the aliphatic alcohols contained in alcoholic beverages might also impair immune cell function, thereby contributing to a further decrease in microbicidal activity. Previous research has shown that aliphatic alcohols inhibit phagocytosis by granulocytes but their effect on human monocytes has not been studied. This is important as they play a crucial role in engulfment and killing of pathogenic microorganisms and a decrease in their phagocytic activity could lead to impaired antimicrobial defence in heavy drinkers. The aim of this study was to measure monocyte phagocytosis following their treatment with those aliphatic alcohols detected in alcoholic beverages. Monocytes were separated from human peripheral blood and phagocytosis of opsonized zymosan particles by monocytes treated with ethanol and aliphatic alcohols individually and in combination was determined. It was shown that these alcohols could suppress the phagocytic activity of monocytes in a concentration-dependent manner and when combined with ethanol, they caused a further decrease in phagocytosis. Due to their additive effects, it is possible that they may inhibit phagocytosis in a clinically meaningful way in alcoholics and episodic heavy drinkers thereby contribute to their increased susceptibility to infectious diseases. However, further research is needed to address this question.

How do methanol and higher alcohols found in alcoholic beverages affect membrane fluidity and migration of granulocytes?

“…Some previous research does show that 1‐propanol, 1‐butanol, and 1‐pentanol can be incorporated into the phospholipid bilayer, just like ethanol, thereby altering the membrane fluidity and migration of granulocytes (Tomonaga, Hirota & Snyderman, ; Yuli, Tomonaga & Synderman, ). However, the concentrations of OAAs (9.1–27.3 mM) used in these experiments significantly exceeded the blood levels expected in alcohol abusers (Pál et al, ; Tomonaga, Hirota & Snyderman, ; Yuli, Tomonaga & Synderman, 1982). Consequently, we now ask whether membrane fluidity and migration of granulocytes are affected when cells are treated separately with ethanol, methanol, mixture of OAAs, and mixture of OAAs combined with ethanol at biologically relevant concentrations.…”

“…Some previous research does show that 1-propanol, 1-butanol, and 1-pentanol can be incorporated into the phospholipid bilayer, just like ethanol, thereby altering the membrane fluidity and migration of granulocytes (Tomonaga, Hirota & Snyderman, 1983;Yuli, Tomonaga & Synderman, 1982). However, the concentrations of OAAs (9.1-27.3 mM) used in these experiments significantly exceeded the blood levels expected in alcohol abusers (Pál et al, 2015;Tomonaga, Hirota & Snyderman, 1983;Yuli, Tomonaga & Synderman, 1982).…”

“…It was also shown that 0.04–80.0 mM concentrations of OAAs can be detected in spirits from commercial and noncommercial sources (Lachenmeier & Musshoff, ; Rehm et al, ). As have been described previously, consumption of 71.3 ml spirits containing 40% ethanol and OAAs at concentrations of 0.04–80.0 mM can produce biologically relevant levels of OAAs in blood, in the range of 0.0001–0.116 mM (Pál et al, ). Could these also affect membrane fluidity and granulocyte migration, possibly to an even greater extent than ethanol alone?…”

Commentary: Short-Chain Alcohols Upregulate GILZ Gene Expression and Attenuate LPS-Induced Septic Immune Response

“…We have previously shown that AAs can decrease superoxideanion production by human granulocytes and inhibit phagocytosis by human granulocytes and monocytes in a concentration dependent manner and, when combined with ethanol, they caused a further decrease in phagocytic activity (22)(23)(24). We have found similar effects when granulocytes and monocytes were exposed to metabolites of AAs including formaldehyde, 1-propanal, acetone, 1-butanal, and 2-butanone (25).…”

“…We have found similar effects when granulocytes and monocytes were exposed to metabolites of AAs including formaldehyde, 1-propanal, acetone, 1-butanal, and 2-butanone (25). We have also calculated that blood concentrations of AAs and their metabolites could reach levels sufficient to decrease phagocytosis by granulocytes and monocytes in a clinically meaningful way in heavy users of distilled spirits (24,25). Thus, AAs and their metabolites may contribute to increased susceptibility to infectious diseases (22)(23)(24)(25).…”