IFN-γ versus IL-17: A Battle During Cardiac Autoimmunity Evolution

Abstract

Cardiovascular diseases are the leading global cause of death. Cardiomyopathies are the most prevalent forms of heart failure diseases currently. They may have genetic or environmental etiology, and the development of an autoimmune process is essential for the progression of the disease. During an autoimmune response, there is the breakdown of self-tolerance and generation of a T-lymphocytes-mediated cellular autoimmune response and B-lymphocytes-mediated humoral autoimmune response. Lymphocytes perpetuate the autoimmune response throughout the release of cytokines, expansion of autoreactive clones, and attenuation of regulatory mechanisms. Increasing evidences indicate that interferon (IFN)-γ and interleukin (IL)-17 participate during autoimmune disorders development. The use of autoimmune cardiomyopathy models revealed antagonistic functions for both cytokines during the evolution of autoimmune cardiomyopathy: while enhanced IFN-γ levels are associated to a lower disease severity, the levels of IL-17 are inversely correlated to a favorable prognosis. More precisely, recent findings indicate that the IFN-γ/IL-17 ratio in combination with other cytokine levels dictates heart's autoimmunity development and dilatation. In this chapter, we discuss the role played by the autoimmune response in the development of cardiomyopathy. We also discuss some immune mechanisms focused on IFN-γ and IL-17's ability to induce and perpetuate cardiac autoimmunity.

High Serum Level of IL-17 in Patients with Chronic Obstructive Pulmonary Disease and the Alpha-1 Antitrypsin PiZ Allele

“…This is confirmed by the observation that when inflammation subsides, the expression of IFN-γ remains at relatively high level despite the prominent decrease in the expression of other proinflammatory cytokines [26]. This may be related to Th17 ability to switch the production from IL-17 to IFN-γ [25]. Consequently, we calculated the IL-17/IFN-γ ratio, which was proposed by some researchers as an unfavorable marker of inflammatory disease progression [25,27].…”

“…This may be related to Th17 ability to switch the production from IL-17 to IFN-γ [25]. Consequently, we calculated the IL-17/IFN-γ ratio, which was proposed by some researchers as an unfavorable marker of inflammatory disease progression [25,27]. In this study, the IL-17/IFN-γ ratio was significantly elevated in both homozygous and heterozygous PiZ allele carriers.…”

“…The production of Th17 is suppressed by IFN-γ, which is a proinflammatory cytokine with anti-inflammatory functions, and it possibly participates in resolution of inflammation [24][25][26]. The IL-17/IFN-γ ratio was suggested as a marker for prognosis and severity of inflammatory diseases [25,27]. It was confirmed that A1AT also reduces Th17 cell formation, increasing the CD4+FoxP3+ Treg cell population, in contrast to IFN-γ, which stimulates Th1 formation [28].…”

“…The formation of a Th17 cell subset is initiated by transforming growth factor-(TGF-) β together with the obligatory presence of IL-6 [24]. The production of Th17 is suppressed by IFN-γ, which is a proinflammatory cytokine with anti-inflammatory functions, and it possibly participates in resolution of inflammation [24][25][26]. The IL-17/IFN-γ ratio was suggested as a marker for prognosis and severity of inflammatory diseases [25,27].…”

Association between serum inflammatory biomarkers and atrial low voltage in patients with atrial fibrillation: A phase 1 FIB-MARK study

“…IL-17A, along with IL-17F, IL-21, IL-22, and TNF-α, is secreted by Th17 cells, which are a novel lineage of effector CD4 + T helper lymphocytes, and is linked to the pathogenesis of several inflammatory and autoimmune disease, including autoimmune and dilated cardiomyopathies, by promoting the migration of cardiac fibroblasts [20] . High IL-17 levels are reported in the acute phase of cardiomyopathy, and patients with dilated cardiomyopathy show increased IL-17 levels compared with healthy donors [21] , [22] .…”