Aliphatic alcohols of illegally produced spirits can act synergistically on superoxide-anion production by human granulocytes

Abstract

Context: Aliphatic alcohols present in illegally produced spirits in a large number of low and middle income countries have been implicated in the etiology of chronic liver disease and cirrhosis. Previous studies have confirmed that chronic alcoholism can lead to increased susceptibility to infectious diseases. Reduced superoxide-anion (O2·−) production by granulocytes could provide a mechanism by which antimicrobial defense is impaired in alcoholics. In vitro experiments have also demonstrated that ethanol can inhibit granulocyte O2·− generation. Aliphatic alcohols consumed as contaminants of illicit spirits may also influence O2·− production thereby contributing to a decrease in microbicidal activity.Objective: The aim of this study was to investigate this possibility. It measured the O2·− production by human granulocytes following treatment of the cells with aliphatic alcohol contaminants found in illicit spirits.Materials and methods: Granulocytes were isolated from human buffy coats with centrifugal elutriation and then treated with individual aliphatic alcohols and their mixture. The O2·− production was stimulated with phorbol-12-13-dibutyrate and N-formyl-methionyl-leucyl-phenylalanine (FMLP) and measured by superoxide dismutase inhibitable reduction of ferricytochrome c.Results: Aliphatic alcohols of illegally produced spirits inhibited the FMLP-induced O2·− production in a concentration dependent manner. They suppressed O2·− generation at 2.5–40 times lower concentrations when combined than when tested individually.Discussion and conclusion: Aliphatic alcohols found in illegally produced spirits can inhibit FMLP-induced O2·− production by granulocytes in a concentration-dependent manner. Due to their synergistic effects, it is possible that, in combination with ethanol, they may inhibit O2·− formation in heavy episodic drinkers.