Involvement of Cytokines in the Pathogenesis of Salt and Water Imbalance in Congestive Heart Failure.

Zaher S Azzam,Emad Khoury,Safa Kinaneh,Reem Ismael-Badarneh,Zaid Abassi,Fadel Bahouth

doi:10.3389/fimmu.2017.00716

Abstract

Congestive heart failure (CHF) has become a major medical problem in the western world with high morbidity and mortality rates. CHF adversely affects several systems, mainly the kidneys and the lungs. While the involvement of the renin–angiotensin–aldosterone system and the sympathetic nervous system in the progression of cardiovascular, pulmonary, and renal dysfunction in experimental and clinical CHF is well established, the importance of pro-inflammatory mediators in the pathogenesis of this clinical setting is still evolving. In this context, CHF is associated with overexpression of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1, and IL-6, which are activated in response to environmental injury. This family of cytokines has been implicated in the deterioration of CHF, where it plays an important role in initiating and integrating homeostatic responses both at the myocardium and circulatory levels. We and others showed that angiotensin II decreased the ability of the lungs to clear edema and enhanced the fibrosis process via phosphorylation of the mitogen-activated protein kinases p38 and p42/44, which are generally involved in cellular responses to pro-inflammatory cytokines. Literature data also indicate the involvement of these effectors in modulating ion channel activity. It has been reported that in heart failure due to mitral stenosis; there were varying degrees of vascular and other associated parenchymal changes such as edema and fibrosis. In this review, we will discuss the effects of cytokines and other inflammatory mediators on the kidneys and the lungs in heart failure; especially their role in renal and alveolar ion channels activity and fluid balance.

Highlights

Congestive heart failure (CHF) has recently become a major medical problem in the developed countries with increased rates of mortality and morbidity, among the elderly popula tion
We have shown that the inflammatory system plays a substantial direct and indirect role in heart failure, this observation does not prove unequivocally a causal role in CHF
Another possibility should be considered, such as that these cytokines are elevated in heart failure in response to the underlying injury, and that they may serve as markers rather than drivers of the disease process

Summary

INTRODUCTION

Congestive heart failure (CHF) has recently become a major medical problem in the developed countries with increased rates of mortality and morbidity, among the elderly popula tion. Autoantibodies, nitric oxide (NO), and endothelin-1 are thought to be relevant to the pathogenesis of CHF [8] It was shown in patients with acute decompensated heart failure (ADHF) that following standard treatment of ADHF, the monocyte profile and circulating inflammatory markers (C-reactive protein and IL-6) shifts to more closely resemble those of healthy controls, suggesting the contribution of systemic inflammation to the pathophysiology of ADHF [9]. We and others have shown the deleterious consequences of heart failure on the lungs and the kidneys; we decided in this review to focus on the effects of cytokines and other inflammatory mediators on the lungs and the kidneys in heart failure; especially their role in renal and alveolar ion channels activity and fluid balance

THE CONTRIBUTION OF THE IMMUNE SYSTEM TO HEART FAILURE

Pulmonary System

Renal System

Effects of Cytokines on Renal Handling of Water and Salt

Findings

SUMMARY AND CONCLUSION