Quantity of alcohol drinking positively correlates with serum levels of endotoxin and markers of monocyte activation

Suthat Liangpunsakul,Wanzhu Tu,Laura E Heathers,Tobyn Linton,Li Wang,Ruth A Ross,Claudie Jimenez,Darrin Mangiacarne,Kristina Chandler,Adepeju Oshodi,Elizabeth Modlik,Breann Mcgee,Evelyn Toh,X Charlie Dong,David E Nelson

doi:10.1038/s41598-017-04669-7

Abstract

It is unknown if LPS (lipopolysaccharides) and markers of immune activation, soluble CD14 (sCD14) and CD163 (sCD163) are associated with the quantity of alcohol consumption. 148 subjects were enrolled (97 excessive drinkers (ED) and 51 controls). Time Line Follow-Back questionnaire was used to quantify the amount of alcohol consumed. Serum LPS, sCD14, and sCD163 were measured. Peripheral blood mononuclear cells (PBMCs) were also isolated. Compared to controls, ED had higher total drinks in the past 30 days, higher levels of LPS, sCD14 and sCD163. The levels of serum LPS, sCD14, and sCD163 were higher among ED with recent alcohol consumption (last drink <10 days before enrollment) compared to those without recent drinking. Similar bacterial genome copy numbers were detected in control and ED groups. We found that ethanol primed PBMCs for LPS-induced inflammatory responses. A positive correlation between serum LPS, sCD14, sCD163 and the quantity of alcohol drinking was observed after adjusting for covariates and that abstinence was associated with decline in the levels of LPS, sCD14 and sCd163. We found an increase in the levels of LPS and markers of monocyte activations in ED. Further studies are needed to determine whether these can be used as the biomarkers for excessive alcohol use.

Highlights

Endotoxin is the key factor in the pathogenesis of alcohol-induced liver injury in rodent models of acute or chronic alcohol consumption as well as in humans[1, 2]
Knowledge, this study was conducted to determine: (i) the effect of chronic alcohol drinking on serum LPS levels and markers of monocyte activation in two well characterized cohorts of human subjects with and without excessive alcohol use, (ii) whether excessive alcohol use sensitizes monocyte to LPS stimulation, (iii) the relationship between serum LPS and soluble CD14 (sCD14)/sCD163 in human subjects with and without excessive alcohol use, (iv) the levels of circulating bacteria, using 16s rDNA in subjects with and without excessive alcohol use, (v) the relationship between serum LPS and markers of monocyte activation and the quantity of alcohol consumption during the last 30 days, and (vi) the levels of serum LPS and markers of monocyte activation in response to alcohol abstinence
We found that the levels of serum LPS, sCD14, and sCD163 were significantly higher in excessive drinkers with recent drinking when compared to those without recent drinking (LPS 5.3 ± 1.2 vs. 3.9 ± 0.8 EU/ml, sCD14 4,030 ± 1722 vs. 2665 ± 1233 ng/ml, and sCD163 4.4 ± 1.6 vs. 2.4 ± 1.4 pg/ml, p < 0.001, Supplementary Table 1)

Summary

Introduction

Endotoxin (or lipopolysaccharides, LPS) is the key factor in the pathogenesis of alcohol-induced liver injury in rodent models of acute or chronic alcohol consumption as well as in humans[1, 2]. LPS can bind to the toll-like receptors (TLRs) on many cell types, notably monocytes and macrophages, leading to the activation of inflammatory cytokines[3]; many of which can be used as surrogates for monocyte activation. A soluble form of this receptor, sCD163, is shed into the circulation upon monocyte activation[4]. CD14 is a pattern recognition receptor on monocytes This glycoprotein acts as a co-receptor with TLRs for the detection of bacterial LPS and has membrane-bound (mCD14) and soluble (sCD14) forms . Another report indicated opposite effects of acute and chronic alcohol on LPS-induced monocyte inflammation[8]. Knowledge, this study was conducted to determine: (i) the effect of chronic alcohol drinking on serum LPS levels and markers of monocyte activation (sCD14 and sCD163) in two well characterized cohorts of human subjects with and without excessive alcohol use, (ii) whether excessive alcohol use sensitizes monocyte to LPS stimulation, (iii) the relationship between serum LPS and sCD14/sCD163 in human subjects with and without excessive alcohol use, (iv) the levels of circulating bacteria, using 16s rDNA in subjects with and without excessive alcohol use, (v) the relationship between serum LPS and markers of monocyte activation and the quantity of alcohol consumption during the last 30 days, and (vi) the levels of serum LPS and markers of monocyte activation in response to alcohol abstinence

Methods

Results

Conclusion