Differential Stat5 Activation and Phenotypic Marker Expression by Immune Cells Following Low Levels of Ethanol Consumption in Mice

Abstract

Ethanol has been recognized as an immunosuppressive agent for many years. Effects of high levels of ethanol consumption on immune functions have been extensively studied, but little is known about the effects of low levels (scuh as 5% ethanol) of ethanol consumption. Herein we report that exposure of mice to 5% ethanol for 4-8 weeks decreases IL-2-augmented splenic NK cell activity, decreases the numbers of NK cells in spleen and liver, decreases the number of granulocytes (Gr-l+) in bone marrow and spleen, and decreases the percentages of B cells in liver. In contrast, the percentages of CD4+CD8+ thymocytes, CD4+CD8- splenocytes, CD4+CD8- liver nonparenchymal cells, CD3+ splenocytes, and CD3+ bone marrow cells were increased. Furthermore, exposure to 5% ethanol increases STAT5 activation in T cells and liver cells while decreases STAT5 activation in NK cells. Taken together, these findings suggest that low levels of ethanol consumption can differentially modulate immune cells in thymus, spleen, bone marrow and liver, which may be due to differential regulation of STAT5 activation by ethanol.

Altered Expression of Cytokine Signaling Pathway Genes in Peripheral Blood Cells of Alcohol Dependent Subjects: Preliminary Findings

“…Chronic exposure to low levels of EtOH results in decreased expression and activation of STAT5 in NK cells and decreased NK cell number in mice (Guo et al., ), and Stat5a/b knockout mice completely lack NK cells, and T‐cells fail to respond to IL‐2 proliferation signals (Moriggl et al., ). These mice also show profound deficits in mast cell proliferation and survival (Shelburne et al., ).…”

A Longitudinal Analysis of Circulating Stress‐Related Proteins and Chronic Ethanol Self‐Administration in Cynomolgus Macaques

“…Rats fed an ethanol diet (≤49 days) showed reduced STAT4 protein and T‐bet mRNA (liver; Ronis et al., 2008). Chronic (4 to 8 weeks) ethanol in mice increased STAT5 activation in T cells and liver, but decreased STAT5 in natural killer cells (Guo et al., 2002). Additional studies are needed to characterize the effects of ethanol on NF‐κB and JAK/STAT signaling with respect to dose, duration of exposure, and cell type, as well as species differences.…”

Mechanisms of alcohol‐induced hepatic fibrosis

“…27 Chronic alcohol consumption has been shown to decrease NK cell activity and numbers. 28,29 Decreased NK activity has also been reported in human alcoholics. 27 Acute ethanol exposure markedly suppresses IFN-␤ and IFN-␥ activation of STAT1 signaling pathways in primary hepatocytes.…”