Increase of plasma IL-9 and decrease of plasma IL-5, IL-7, and IFN-γ in patients with chronic heart failure

Abstract

BackgroundSeveral cytokines are associated with the development and/or progression of chronic heart failure (CHF). Our aim was to look more closely at the cytokine networks involved in CHF, and to assess whether disease etiology affects cytokine expression. The study population was comprised of a) 69 patients with stable CHF, New York Heart Association (NYHA) II/IV classes, secondary to ischaemic (ICM) and non ischaemic dilated (NIDCM) cardiomyopathy and b) 16 control subjects. We analyzed and compared the plasma levels of 27 pro- and anti-inflammatory mediators, in the study population and assessed for any possible correlation with echocardiographic parameters and disease duration.Methods27 cytokines and growth factors were analyzed in the plasma of ICM- (n = 42) and NIDCM (n = 27) NYHA class II-IV patients vs age- and gender-matched controls (n = 16) by a beadbased multiplex immunoassay. Statistical analysis was performed by ANOVA followed by Tukey post-hoc test for multiple comparison.ResultsMacrophage inflammatory protein (MIP)-1β, Vascular endothelial growth factor (VEGF), interleukin (IL)-9, Monocyte chemotactic protein (MCP)-1, and IL-8 plasma levels were increased in both ICM and NIDCM groups vs controls. In contrast, IL-7, IL-5, and Interferon (IFN)-γ were decreased in both ICM and NIDCM groups as compared to controls. Plasma IL-6 and IL-1 β were increased in ICM and decreased in NIDCM, vs controls, respectively.IL-9 levels inversely correlated, in ICM patients, with left ventricular ejection fraction (LVEF) while IL-5 plasma levels inversely correlated with disease duration, in NYHA III/IV ICM patients.This is the first time that both an increase of plasma IL-9, and a decrease of plasma IL-5, IL-7 and IFN-γ have been reported in ICM as well as in NIDCM groups, vs controls. Interestingly, such cytokines are part of a network of genes whose expression levels change during chronic heart failure. The altered expression levels of MIP-1 β, VEGF, MCP-1, IL-1 β, IL-6, and IL-8, found in this study, are in keeping with previous reports.ConclusionsThe increase of plasma IL-9, and the decrease of plasma IL-5, IL-7 and IFN-γ in ICM as well as in NIDCM groups vs controls may contribute to get further insights into the inflammatory pathways involved in CHF.

Increased Systemic and Local Interleukin 9 Levels in Patients with Carotid and Coronary Atherosclerosis

“…However, the role of IL-9 in cardiovascular disorders is largely unknown. Increased plasma IL-9 has been reported in patients with ischemic and non-ischemic cardiomyopathies, inversely correlated with parameters of impaired left ventricular function [13], and increased serum IL-9 has also been reported in 45 patients with acute ischemic stroke of different etiology [25]. However, the present study is, to the best of our knowledge, the first report of increased levels of IL-9 in patients with confirmed coronary and carotid atherosclerosis.…”

“…While IL-9 has been implicated as a pathogenic mediator of asthma and allergic disorders, recent studies suggest that IL-9 may enhance as well as dampen the progression of various autoimmune disorders [9]–[12]. Increased plasma levels of IL-9 are seen in patients with heart failure, possibly correlated to disease progression [13], and increased IL-9 levels have been reported in experimental cardiomyopathy [14]. IL-9 has also been shown to facilitate Th17 cell expansion, and to stimulate production of IL-17 from mononuclear cells of both healthy and diseased subjects such as patients with psoriasis [15].…”

Dietary fatty acids alter left ventricular myocardial gene expression in Wistar rats

“…Represented Canonical Pathways relevant to nonischemic cardiomyopathy included sphingosine-1-phosphate signaling,[19] relaxin signaling,[20] Gα12/13 signaling[21] and CXCR4 signaling[22] (WES+DHA vs. CON), as well as ILK signaling,[23] actin cytoskeleton signaling[24] and IL-9 signaling[25, 26] (WES+DHA vs. WES). Toxicological pathways relevant to nonischemic cardiomyopathy included p53 signaling[27, 28] and NRF2-mediated oxidative stress response[29] (WES+DHA vs. CON, WES+DHA vs. WES), as well as RAR activation[30, 31] (WES+DHA vs. CON) and cardiac hypertrophy (WES+DHA vs. WES).…”

“…[24] The cytokine IL-9 was also identified as relevant to the WES versus WES+DHA comparison; circulating levels are increased in association with cardiomyopathy and heart failure. [25, 26]…”

The Role of B-Cells in Heart Failure

“…One role is the interaction with T-cells, specifically T helper (Th1) cells, to stimulate the production of circulating cytokines, which can affect contractility as well as adverse remodeling and have a great impact on prognosis and outcomes. [12][13][14][15] Even though the interaction with T-cells remains important for the production of cytokines, B-cells also can act in a T-cell independent way. This observation is supported by recent findings from our group demonstrating that nude/athymic (nu-nu) mice, which lack T-cells, develop a severe, acute CMP similar to that observed in wild-type mice in a nonischemic CMP mouse model (unpublished data).…”