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

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.

The Correlation of Central Serous Chorioretinopathy and Subsequent Cardiovascular Diseases of Different Types: A Population-Based Cohort Study

“…The primary function of aldosterone is to export excessive fluid and sodium to maintain body homeostasis via the activation of mineralocorticoid receptors [21]. If the aldosterone pathway was altered, fluid would be retained in the body and lead to congestive heart failure and secondary hypertension [22,23], which could occur in the choroidal vascular structure in patients with retinal venous occlusion and CSC via the inappropriate activation of mineralocorticoid receptors and related choroidal vasodilation [13,24]. In addition to the fluid-sodium pathway, elevated platelet aggregation and hypercoagulability were also found in patients with CSC in previous research [25].…”

Cytokine–Ion Channel Interactions in Pulmonary Inflammation

“…The reported Western world life time risk is typically about 33% for men and 29% for women for our population, and depends, besides sex, on comorbidities and cardiovascular risk factors, such as arterial hypertension, diabetes, obesity, sleep related disorders, smoking, sedentary lifestyle, and ethnic background ( 20 ). In patients aged 65 years and older, more than 10% suffer from congestive heart failure ( 21 ). Interstitial pulmonary edema and alveolar flooding impair lung mechanics and gas exchange, thus causing dyspnea and tachypnea, which ultimately results in an age-dependent in-hospital mortality rate of about 15% ( 22 ).…”

“…A second hypothesis postulates that the failing, but not the healthy, heart has the ability to produce pro-inflammatory TNF during dilated myopathy. Third, decreased cardiac output could cause systemic tissue hypoxia with subsequent systemic inflammation, which might be the primary stimulus for increased TNF production ( 21 ).…”

“…Soluble TNF receptor-1 and interleukin-8 (IL-8) are independently associated with cardiovascular mortality, as is endothelin-1. In transgenic mice overexpressing TNF the left ventricular ejection fraction was depressed depending on TNF gene dosage ( 21 ). TNF has been associated with worsened prognosis.…”

“…Similar results were observed with the neutralizing antibody infliximab ( 28 ). Whether the negative results are explained by inappropriate blocking of a “physiological” inflammation linked with tissue-reparative processes such as cardiac remodeling, or whether other mechanisms like too advanced heart failure, infections, toxicity of treatment, or genetic polymorphisms are involved, remains open, and should be further studied ( 21 ). Recently, it was suggested that beneficial or detrimental effects of TNF neutralizing agents depend on whether they spared or rather blunted discrete amounts of TNF that preconditioned cardiomyocytes to make them more resistant to high concentrations of the cytokine ( 29 ).…”