Cytokines and acute heart failure

Methodist DeBakey Heart Center, The Methodist Hospital, Houston, TX, USA.
Critical care medicine (Impact Factor: 6.31). 02/2008; 36(1 Suppl):S9-16. DOI: 10.1097/01.CCM.0000297160.48694.90
Source: PubMed


In patients with chronic heart failure, ongoing myocardial injury partially results from activation of the inflammatory system, with production and release of proinflammatory cytokines, activation of the complement system, production of autoantibodies, overexpression of major histocompatibility complex molecules, and expression of adhesion molecules that may perpetuate the inflammatory state. Acute decompensated heart failure modifies the course of chronic heart failure and worsens outcomes via a combination of potential mechanisms, including neurohormonal activation, apoptosis, and the inflammatory cascade. Proinflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6, play a pathogenetic role in chronic heart failure, and anti-inflammatory immune therapy is currently under investigation. In acute decompensation of chronic heart failure, the change in the inflammatory cytokine activation cascade is less clear. Larger investigational studies are needed to assess the exact roles of circulating and intracardiac cytokines in this particular patient population.

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    • "IL-6 is involved in the development of atherosclerosis, myocardial remodeling, and experimental and clinical cardiac dysfunction [58,59]. The inflammatory cytokines IL-6 and TNF-α, are known to promote LV dysfunction and play a pathogenic role in heart failure and DCM [51,53,60]. Moreover, HO-1 plays a critical protective role during the development of inflammation in the cardiovascular system [61,62]. "
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    ABSTRACT: Heme oxygenase-1 (HO-1) has been implicated in cardiac dysfunction, oxidative stress, inflammation, apoptosis and autophagy associated with heart failure, and atherosclerosis, in addition to its recognized role in metabolic syndrome and diabetes. Numerous studies have presented contradictory findings about the role of HO-1 in diabetic cardiomyopathy (DCM). In this study, we explored the role of HO-1 in myocardial dysfunction, myofibril structure, oxidative stress, inflammation, apoptosis and autophagy using a streptozotocin (STZ)-induced diabetes model in mice systemically overexpressing HO-1 (Tg-HO-1) or mutant HO-1 (Tg-mutHO-1). The diabetic mouse model was induced by multiple peritoneal injections of STZ. Two months after injection, left ventricular (LV) function was measured by echocardiography. In addition, molecular biomarkers related to oxidative stress, inflammation, apoptosis and autophagy were evaluated using classical molecular biological/biochemical techniques. Mice with DCM exhibited severe LV dysfunction, myofibril structure disarray, aberrant cardiac oxidative stress, inflammation, apoptosis, autophagy and increased levels of HO-1. In addition, we determined that systemic overexpression of HO-1 ameliorated left ventricular dysfunction, myofibril structure disarray, oxidative stress, inflammation, apoptosis and autophagy in DCM mice. Furthermore, serine/threonine-specific protein kinase (Akt) and AMP-activated protein kinase (AMPK) phosphorylation is normally inhibited in DCM, but overexpression of the HO-1 gene restored the phosphorylation of these kinases to normal levels. In contrast, the functions of HO-1 in DCM were significantly reversed by overexpression of mutant HO-1. This study underlines the unique roles of HO-1, including the inhibition of oxidative stress, inflammation and apoptosis and the enhancement of autophagy, in the pathogenesis of DCM.
    Full-text · Article · Sep 2013 · PLoS ONE
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    • "Augmented cytokine secretion is likely in the AHF setting, due to congestion-induced inflammatory activation [4] [5]. Indeed, higher circulating levels of TNF-a, IL-1b, IL- 4 and IL-6 than in healthy controls have been reported in AHF patients (reviewed in [6] [7]). "
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    ABSTRACT: Aims: The aim of this study was to gain insight in the inflammatory response in acute heart failure (AHF) by assessing (1) plasma cytokine profiles and (2) prognostic value of circulating cytokines in AHF patients. Methods and results: Plasma levels of 26 cytokines were quantified by multiplex protein arrays in 36 patients with congestive AHF, characterized by echocardiographic, radiologic, and clinical examinations on admission, during hospitalization and at discharge. Recurrent AHF leading to death or readmission constituted the combined end point, and all patients were followed for 120 days after discharge. Levels of 15 of the measured cytokines were higher in AHF than in healthy subjects (n=22) on admission. Low levels of MCP-1, IL-1β and a low IL-1β/IL-1ra ratio predicted fatal and non-fatal AHF within 120 days. Patients with low circulating levels of IL-1β had lower left ventricular ejection fraction and higher levels of N-terminal pro-B-type natriuretic peptide, while patients with low levels of MCP-1 had higher E/E' and inferior caval vein diameter, than patients with high levels. Conclusion: Immune activation, reflected in increased cytokine levels, is present in AHF patients. Interestingly, failure to increase secretion of IL-1β and MCP-1 during AHF is associated with poor outcome.
    Full-text · Article · Feb 2013 · Cytokine
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    • "When patients were classified by plasma norepinephrine levels, only those patients with plasma norephinephrine levels >400 pg/mL had statistically significant differences in these markers as compared to normal controls [50]. Other studies have shown correlations between plasma levels of angiotensin II, endothelin, and von Willebrand factor [51] [52]. "
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    ABSTRACT: Thrombotic events (coronary thrombosis, venous thromboembolism, intraventricular thrombosis, intracranial and systemic thromboembolism) occur frequently in patients with heart failure. These events may be precipitated by several mechanisms including hypercoagulability through enhancement of procoagulant reactions, impairment of the protein C pathway, protease activated receptor (PAR) activation, adenosine-mediated thrombosis, or neurohormonal activation; stasis secondary to low cardiac output; and endothelial dysfunction from neurohormonal activation or systemic inflammation. Pathophysiologic evidence and analyses of retrospective data support the hypothesis that antithrombotic agents may improve outcomes in patients with heart failure. Warfarin has not been shown to reduce clinical events in patients with heart failure, although several of the completed randomized trials were underpowered, and the most recent was not placebo-controlled. Many unanswered questions remain that justify continued research in this area. This paper examines the conceptual framework, opportunities, and challenges of clinical investigative approaches with the newer anti-thrombotic agents in patients with heart failure. Critical questions are raised with regard to clinical trial designs that warrant consideration as the field progresses.
    Full-text · Article · Jan 2013 · International journal of cardiology
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