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Excessive drinking can lead to the development of immune dysfunction. Our aim is to investigate the effect of alcohol on immune activation from circulating peripheral blood monocytes in excessive drinkers (EDs). Twenty-two EDs and healthy controls were enrolled. Time line follow-back was used to quantify the amount of alcohol consumed in the past 30 days before enrollment. Peripheral blood-derived CD14+ monocytes were isolated for gene expression analyses. Serum interleukin (IL)-6, IL-10 and lipopolysaccharides (LPS) were also measured. We found that serum LPS concentrations were significantly higher in EDs compared with controls (P<0.05). While no differences in the levels of circulating IL-6 and IL-10 were observed, the relative levels of gene transcripts (RQ) for Il6 (an M1-polarizing cytokine) and Il10 (an M2-polarizing cytokine) were significantly higher in peripheral blood-derived monocytes from EDs compared with controls (Il6: P<0.01. Il10: P<0.05). EDs exhibit early immune activation of peripheral blood monocyte mRNA transcripts, notably Il6 and Il10. Future studies are needed to explore the clinical implications of our findings and determine whether the levels of Il6 and Il10 mRNA expression can be used to identify those with excessive drinking and to monitor for alcohol abstinence.