Prognostic Significance of the Systemic Inflammatory and Immune Balance in Alcoholic Liver Disease with a Focus on Gender-Related Differences.

Beata Kasztelan-Szczerbińska,Krzysztof Celiński,Sławomir Miącz,Agnieszka Zwolak,Agata Surdacka,Jacek Roliński,Mariusz Szczerbiński,Golo Ahlenstiel

doi:10.1371/journal.pone.0128347

Beata Kasztelan-Szczerbińska, Krzysztof Celiński + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0128347

Copy DOI

Abstract

ObjectivesMechanisms of immune regulation in alcoholic liver disease (ALD) are still unclear. The aim of our study was to determine an impact of Th17 / regulatory T (Treg) cells balance and its corresponding cytokine profile on the ALD outcome. Possible gender-related differences in the alcohol-induced inflammatory response were also assessed.Materials and Methods147 patients with ALD were prospectively recruited, assigned to subgroups based on their gender, severity of liver dysfunction and presence of ALD complications at admission, and followed for 90 days. Peripheral blood frequencies of Th17 and Treg cells together with IL-1beta, IL-6, IL-17A, IL-23, and TGF-beta1 levels were investigated. Flow cytometry was used to identify T cell phenotype and immunoenzymatic ELISAs for the corresponding cytokine concentrations assessment. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications.ResultsIL-17A, IL-1beta, IL-6 levels were significantly increased, while TGF-beta1 decreased in ALD patients. The imbalance with significantly higher Th17 and lower Treg frequencies was observed in non-survivors. IL-6 and TGF-beta1 levels differed in relation to patient gender in ALD group. Concentrations of IL-6 were associated with the severity of liver dysfunction, development of ALD complications, and turned out to be the only independent immune predictor of 90-day survival in the study cohort.ConclusionsWe conclude that IL-6 revealed the highest diagnostic and prognostic potential among studied biomarkers and was related to the fatal ALD course. Gender-related differences in immune regulation might influence the susceptibility to alcohol-associated liver injury.

Highlights

Alcoholic liver disease remains a major health problem worldwide and its prevalence is increasing in Eastern, as well as some Western countries
IL-17A, IL-1beta, IL-6 levels were significantly increased, while TGF-beta1 decreased in alcoholic liver disease (ALD) patients
Concentrations of IL-6 were associated with the severity of liver dysfunction, development of ALD complications, and turned out to be the only independent immune predictor of 90-day survival in the study cohort

Summary

Introduction

Alcoholic liver disease remains a major health problem worldwide and its prevalence is increasing in Eastern, as well as some Western countries Significant progress has been made in our understanding of the role of inflammatory activation and immune dysregulation in deterioration of the disease course and its outcome. It is widely accepted that both acute and chronic ethanol consumption alters the immune system function [3, 4, 5, 6]. Ethanol may impair antigen presentation by monocytes and dendritic cells, interfere with the expression of adhesion molecules and decrease T cell proliferation [7]. In parallel with ALD progression and increasing synthesis of pro-inflammatory cytokines/ chemokines by Kupffer cells, an immune response towards antigens derived from damaged hepatocytes and massive inflammatory cell recruitment into the liver may occur [8]

Objectives

Methods

Results

Conclusion