Major Interleukins: Role in the Pathogenesis of Atrial Fibrillation

Abstract

Interleukins (IL) are a group of cytokines with complex immunomodulatory functions, whereas atrial fibrillation (AF) is the most common cardiac arrhythmia. This review article highlights the role of major IL in the pathogenesis of AF. IL-1 had elevated levels in permanent and persistent AF patients as compared to paroxysmal AF. A study had shown a straightforward connection between the development of postoperative atrial fibrillation and IL-2 sera levels shortly after cardiopulmonary bypass graft for the first time. IL-4 has been involved in anti-inflammatory response and played no role in the contribution of AF. The elevated level of IL-6 rapidly induces atrial electrical remodeling by downregulating cardiac connexins. This change could be significantly increased the risk of AF and related complications during active inflammatory processes. Moreover, a study has shown higher IL-8 levels in permanent AF patients as compared with paroxysmal AF patients. An association was found between IL-10 gene -592A/C polymorphism and AF in Han Chinese. Recombinant human IL-11 therapy shortened atrial refractoriness and also created favorable conditions for AF by an indirect mechanism involving volume expression, stretching of atrial myocardial tissue and sodium retention. An elevated IL-12 expression was observed in the left atrial tissues of AF patients. IL-17 signaling pathway has played a significant role, and some genes could be used as potential therapeutic targets for AF. An association between the risk of AF with single nucleotide polymorphism of IL-18 and also resulted in the increased left atrial diameter and decreased left ventricular ejection fraction in AF subjects as compared to control. IL-27 genetic variants had increased the occurrence of AF. AF patients had elevated levels of IL-37 that were closely linked with AF subgroups.