Mechanism of Inhibition of Granulopoiesis by Ethanol

Ethanol-induced neutrophil apoptosis is mediated through nitric oxide

“…Moreover, in in vitro studies, exposure of myeloid precursors to clinically relevant ethanol concentrations inhibited the production of granulocyte colonies [5,9]. Other investigators suggest that ethanol suppresses the growth of myeloid precursors directly, as well as through the inhibition of the production of cytokines such as TNF and G-CSF [34,35].…”

“…However, the occurrence of ethanol-associated neutropenia has been reported in only a limited number of cases and more so during acute intoxication in chronic alcoholics [5,6]. We hypothesize that ethanol ingestion induces neutropenia by accelerating the apoptosis of neutrophils.…”

“…On the contrary, at a higher concentration of ethanol (during acute ethanol intoxication), both the rates of apoptosis and clearance of apoptosed cells may not only be faster but may also be greater than the transfer rate of neutrophils from the reservoir pool of neutrophils. Furthermore, Tisman and Herbert and other investigators report that ethanol in concentrations commonly observed in the blood of chronic alcoholics inhibits the proliferation of myeloid precursors [5,9,10]; this effect of ethanol has been shown to contribute to the depletion of the neutrophil reservoir (myeloid precursors in the bone marrow) in chronic alcoholics [5,9,10]. We propose that there may not be any neutrophil reservoir in chronic alcoholics (neither adherent neutrophils to the vascular endothelium nor myeloid precursors in the bone marrow) to compensate for acute ethanol intake-induced accelerated loss of peripheral blood neutrophils; hence, acute alcohol intoxication in chronic alcoholics may manifest in the form of neutropenia.…”

“…Ethanol may alter the host defense status in multiple ways including liver injury, malnutrition, and deranged leukocyte function [6,13,14]. In addition to neutropenia [1][2][3][4][5], acute ethanol intoxication has been observed to decrease neutrophil mobilization to sites of inflammation [15]. In addition, ethanol decreased the adherence of neutrophils to endothelial cells in a dose-dependent manner in both in vitro and in vivo studies [16,17].…”

“…Ethanol ingestion has been associated with neutropenia in humans [1][2][3][4][5]. However, the occurrence of ethanol-associated neutropenia has been reported in only a limited number of cases and more so during acute intoxication in chronic alcoholics [5,6].…”