The role of interleukins in pathogenesis and prognosis of atrial fibrillation

ABSTRACT

Introduction

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Moreover, it is mentioned as one of the important causes of death due to heart disease, which imposes an undeniable financial burden on public health systems. Almost 1 out of 4 individuals aged 40 to 55 will experience AF at some point during their life. Increasing the pressure or the volume of the atria over time leads to the activation of fibroblasts, resulting in the accumulation of extracellular matrix and fibrosis. By disturbing electrical conduction, fibrosis creates microreentrant circuits, which can develop into AF.

Areas covered

In this article, we evaluated the vital role of interleukins and inflammatory mediators in the pathogenesis, prognosis, and treatment of AF. We also discussed the importance of the broader use of interleukins in the clinical management of AF patients.

Expert opinion

Interleukins and inflammatory markers can be used as markers of diagnosis, cardiovascular events, and mortality in AF patients. Finally, the utilization of substances upregulating IL-10, such as resolvin D1 (RvD1), or applying IL-6 down-regulators and inhibitors, including anti-IL-6 antibodies, colchicine, and C1q/tumor necrosis factor-related protein-9 (CTRP9), are effective in the reduction of atrial interstitial fibrosis and treating AF patients.

Summary

Interleukins are mediators of the immune system, which play vital roles, directly or indirectly, in many immune responses and have a wide range of effects on the systems in the body. Similarly, these interleukins can have versatile roles in igniting or attenuating cardiovascular disorders. However, due to the complexity and variability of their effects on the cardiovascular system, research is still ongoing to capture a complete and realistic image of the role of interleukins in the development of cardiovascular disorders. Atrial fibrillation occurs following the irregular rhythm of the beat in the atria. Subsequently, the normal blood flow from the atria to the ventricles will be disturbed. Atrial fibrillation is the most common heart arrhythmia that might need medical care. However, the probability of severe atrial fibrillation outcomes or symptoms is higher in people with underlying comorbidities. This review investigates the role of interleukins in the occurrence of atrial fibrillation and its long-term complications. Atrial fibrillation usually begins as occasional brief episodes that start and stop spontaneously, but it can progress to more persistent forms that are associated with an increased risk of stroke and heart failure.. Interleukins and inflammatory mediators can enhance atrial fibrillation by worsening the conductance of the electrical signal and by boosting the fibrogenesis and structural remodeling of the atria. Currently, based on the role of interleukins in atrial fibrillation, therapeutic methods are being developed to prevent and attenuate its serious consequences. These therapeutic methods can impressively affect and improve the lives of millions of people suffering from this disorder.

KEYWORDS:

• Atrial fibrillation
• diagnosis
• fibrosis
• inflammation
• inflammatory mediators
• interleukins
• prognosis

Article highlights

• Inflammatory mediators influencing AF development and prognosis include CRP, IL-6, NLRP3 inflammasome, and IL-17 which can determine the risk of thromboembolism, stroke, the outcome of cardioversion, and mortality in AF patients.

• Targeting inflammatory pathways, for instance by the administration of anti-IL-6 antibodies, IL-10, and colchicine can lead to a reduction in the risk of atrial interstitial fibrosis based on preclinical and clinical studies.

• Targeting inflammatory pathways, for instance by the administration of anti-IL-6 antibodies, IL-10, and colchicine can lead to a reduction in the risk of atrial interstitial fibrosis based on preclinical and clinical studies.

Acknowledgments

We used Inkscape 1. 2. 1 to create the figure. Parts of the figure and graphical abstract were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.