Elevated plasma levels of Th17-related cytokines are associated with increased risk of atrial fibrillation.

Na Wu,Yafei Li,Bin Xu,He Tang,Yuan Liu,Mengxuan Zhang,Li Zhong,Xinghua Chen,Maoqing Shu,Zhiyuan Song,Long Wu,Ying Xiang

doi:10.1038/srep26543

Abstract

We performed a matched case-control study using a propensity score matching, to assess the association of Th17-related cytokines, including interleukin (IL) 17A (IL-17A), IL-17F, IL-21, IL-22 and IL-6, along with interferon-γ (IFN-γ), IL-10, IL-9, and IL-4, with the risk of AF. A total of 336 patients with AF were matched 1:1 with patients without AF. Plasma levels of cytokines were measured using Luminex xMAP assays. The plasma levels of all examined cytokines were significantly higher in AF patients than controls (P < 0.05), and these cytokines were highly correlated with each other (P < 0.01). A multivariate conditional logistic regression analysis showed that elevated plasma levels of IL-17A, IL-17F, IL-21, IL-22, IFN-γ, IL-10, IL-9 and IL-6 were significantly associated with AF risk independently of potential confounders. There were no significant differences in plasma levels of examined cytokines between paroxysmal and chronic AF patients. IL-17A, IL-21, IL-10 and IL-6 levels were positively correlated with left atrial diameter; IL-17F level was negatively correlated with left ventricle ejection fraction among AF patients (P < 0.05). Elevated plasma levels of Th17-related cytokines were independently associated with increased an risk of AF; hence, Th17-related cytokines may be involved in the pathogenesis of AF.

Highlights

Atrial fibrillation (AF) is the most common type of arrhythmia, accounting for approximately one-third of hospitalizations for cardiac rhythm disturbances
IL-17A, IL-21, IL-10 and IL-6 levels were positively correlated with left atrial diameter (LAD); the IL-17F level was negatively correlated with left ventricle ejection fraction (LVEF) among AF patients
It has been proposed that inflammation has a possible pathogenic link to AF14, but it is still unknown which specific inflammatory cells or which related secreted cytokines contribute to the development of AF

Summary

Introduction

Atrial fibrillation (AF) is the most common type of arrhythmia, accounting for approximately one-third of hospitalizations for cardiac rhythm disturbances. The circulating levels of some inflammatory cytokines including C-reactive protein (CRP) are associated with AF2,3. To the best of our knowledge, which specific inflammatory cells and related cytokines contribute to the development of AF still remains unclear. In the absence of TGF-βbut in the presence of IL-6, IL-1β, and IL-23, alternative Th17 cells produce higher levels of IFN-γ9. Th17 and its related cytokines have been reported to be pathogenic and autoreactive. We conducted a propensity-score matched case-control study to investigate the association of Th17-related cytokines, including IL-17A, IL-17F, IL-21, IL-22 and IL-6, along with IFN-γ, IL-10, IL-9, and IL-4, with the risk of AF. We further compared the differences of plasma levels of all examined cytokines among patients with different clinical types of AF, and examined the correlation of these cytokines with atrial remodeling

Methods

Results

Conclusion