Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines play a pathogenetic role in a variety of infective and inflammatory diseases. In the present study, we had two objectives: (a) to define the kinetics of tumor necrosis factor (TNF) in plasma after acute myocardial infarction (AMI) in patients treated with early thrombolysis, and (b) to measure other cytokines, interleukin-1 (IL-1) and TNF receptor antagonists, in plasma. TNF-alpha, but not IL-1 beta or IL-8, was present in plasma of 6 of 7 patients with severe AMI (Killip class 3 or 4). No TNF (< 50 pg/ml) was detected in a group of 11 patients with uncomplicated myocardial infarction (Killip class 1) or in control patients without AMI. Soluble TNF receptor type I and IL-1 receptor antagonist (IL-1Ra) were also significantly increased in the group with severe AMI compared with those with uncomplicated AMI. Circulating TNF is increased only in AMI complicated by heart failure at hospital admission. This finding may have diagnostic and therapeutic relevance.
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PMID:Cytokines in acute myocardial infarction: selective increase in circulating tumor necrosis factor, its soluble receptor, and interleukin-1 receptor antagonist. 751 19

Elevated tumour necrosis factor alpha (TNF-alpha) has been demonstrated in chronic cardiac failure (CCF) and may relate to severity of CCF and development of cachexia. We measured TNF receptor p55 in addition to TNF-alpha in an attempt to improve the detection rate of TNF-alpha activation, and simultaneously measured interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein. Thirty-four patients with CCF and 24 control subjects were studied. Only TNF receptor p55 [6.95 (0.77-42.3) vs. 5.52 (1.50-13.36) ng mL-1 (median (range)] and IL-6 [0.335 (0-9.79) vs. 0(0-14.71) pg mL-1) were significantly elevated in patients compared with control subjects (both P < 0.05). All inflammatory markers were more frequently elevated in patients, but none correlated with any of the clinical parameters studied. Reasons for inflammatory marker elevation in CCF are uncertain, but future studies should measure the p55 TNF receptor and IL-6 in addition to TNF-alpha, to improve detection of cytokine activity.
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PMID:Cytokine profile in chronic cardiac failure. 895 9

We studied the plasma levels of TNF-alpha, IL-6, IL-8 and soluble adhesion molecules (sE-Selectin, sL-Selectin, sVCAM-1) immediately before and during mechanical circulatory support with a Biventricular Assist Device System (BVAD-"Berlin Heart") in comparison to patients with chronic heart failure (NYHA classes II/III) and patients with coronary artery disease with normal ventricular function. Additionally, the biocompatibility of the membranes used in the "Berlin Heart" was tested in vitro. IL-6 and IL-8 but not TNF-alpha could only be detected in patients with cardiogenic shock immediately before starting circulatory support. Furthermore, plasma concentrations of soluble adhesion molecules were statistically significantly elevated in patients with cardiogenic shock compared to patients with coronary artery disease. This picture of a systemic inflammatory response syndrome without significant level of TNF-alpha looks quite similar to that seen in patients following trauma and severe operations. During mechanical circulatory support plasma levels of cytokines and soluble adhesion molecules dropped to low levels in patients, who were successfully maintained on BVAD. By contrast, we have found persistently elevated levels of these mediators in patients with fatal outcome. This seems not to be the result of individual distinct response of blood cells to contact with the artificial surfaces of the device. In summary, our data suggest the development of a systemic inflammatory response syndrome may be due to hypoxia during cardiogenic shock. Persistence of systemic inflammation suggests failing of the mechanical support. Therefore, the monitoring of inflammatory mediators may be relevant as a prognostic marker in these patients (disappearance of peripheral hypoxia).
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PMID:[Inflammatory mediators in patients with biventricular assist device systems]. 906 44

1 Cytokines may parallel or regulate the beneficial effects of beta-adrenoceptor antagonist treatment observed in chronic heart failure (CHF) patients. Therefore, this study was performed in order to investigate alterations of cytokine levels in beta-blocker-treated patients suffering from CHF. 2 We investigated plasma cytokine levels in eight healthy controls and 12 CHF patients. The patients were treated with standard medication (CHFstd) or with standard medication and additional beta1-blocker metoprolol (CHFmet). Interleukin-(IL)-1alpha, IL-1beta, IL-1 receptor antagonist (IL-1ra), IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF), soluble TNF receptor type 1 (sTNF-R1), sTNF-R2, and sCD14 were measured by ELISA. 3 IL-1alpha and IL-1beta were not detectable in any of the tested groups. IL-2, TNF, or sCD14 were not altered as compared with healthy control subjects. CHFstd patients expressed enhanced IL-1ra, IL-6, IL-8, IL-10, sTNF-R1 and sTNF-R2. In CHFmet patients IL-1ra, IL-6 and IL-8 remained at the same level. In contrast, sTNF-R1 levels were significantly reduced, although not to control, whereas the sTNF-R2 and IL-10 were reduced to control levels. 4 The cAMP levels of mononuclear cells--recalculated for the patients included in this study from previous work [Werner et al. (2001). Basic Res. Cardiol., 96, 290]--correlated inversely with the sTNF-R2 data (Pearson, r = -0.46; P = 0.041; Spearman, r = -0.64, P = 0.002). 5 The present data indicate an interaction of the neurohumoral and the cytokine system in CHF patients at the cAMP level. Thus, measurement and correlation of sTNF-R2 and cAMP may provide a tool useful during investigation of beta-blocker therapy.
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PMID:The enhanced plasma levels of soluble tumor necrosis factor receptors (sTNF-R1; sTNF-R2) and interleukin-10 (IL-10) in patients suffering from chronic heart failure are reversed in patients treated with beta-adrenoceptor antagonist. 1256 25

We studied effects of beta-adrenoblocker carvedilol vs placebo in 60 patients with chronic cardiac failure (CCF) of functional classes III-IV in a 6-month open randomized trial. We examined clinical course, exercise tolerance (a 6 min walk test), endothelial state markers (endothelium-dependent vasodilation, number of circulating endotheliocytes) and activity of systems affecting endothelium (triglycerides, malonic dialdehyde, IL-8, uric acid). The drug was added to conventional therapy (ACE inhibitors, diuretics, cardiac glycosides) in a stable CCF course. Carvedilol group of patients demonstrated a marked trend to reduction of the number of hospitalizations, attenuation of CCF, better tolerance to exercise, lower levels of uric acid (p < 0.05), malonic dialdehyde (p < 0.05) and IL-8 (p = 0.09). There was also wider basal diameter of the brachial artery, and in the diameter at the peak of reactive hyperemia (p = 0.07). The effect was dose-dependent: in patients given 25-50 mg/day of carvedilol there was a trend to a lower circulation of endotheliocytes, triglyceridemia, lipid peroxidation and chronic inflammation. Thus, long-term treatment of CCF with inclusion of standard doses of carvedilol not only improves clinical status of the patients but produces a noticeable endothelioprotective effect.
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PMID:[Endothelial protection in patients with apparent cardiac failure in long-term therapy by carvedilol]. 1293 11

Cytokines and chemokines are believed to play a pathogenic role in heart failure (HF). Although some cytokines and chemokines have been examined in HF, information about others is still lacking. We aimed to examine the expression of cytokines belonging to the interleukin (IL)-6 superfamily [IL-6 and ciliary neurotrophic factor (CNTF)], as well as IL-1beta and the CXC-chemokines monocyte chemoattractant protein-1 (MCP-1) and IL-8. We examined their expression in the heart, lung and spleen during development of postischaemic HF 1 and 6 weeks following left coronary artery ligation. Rats, which after myocardial infarction had a left ventricular end-diastolic pressure above 15 mmHg, were considered to be in HF. Sham-operated rats served as controls. A substantial upregulation of cardiac IL-1beta was measured in HF at 1 week, whereas a downregulation was measured in the lungs. At 6 weeks no altered regulation was seen. CNTF was only upregulated in the viable left ventricle at 6 weeks and IL-6 was upregulated in the infarcted region at 1 week. Cardiac MCP-1 was upregulated in the viable and the infarcted region of the failing left ventricle at 1 week, with the highest expression in the latter. In the lung, another pattern of regulation was seen with a significant increase in pulmonary MCP-1 at 6 weeks. IL-8 was only detected in the infarcted region at 1 week. In the spleen, no regulation of cytokines was found. In conclusion, we report an organ-specific regulation of cytokines and chemokines in postischaemic HF. Our novel findings of increased cardiac CNTF and cardiopulmonary MCP-1 mRNA indicate a role for these factors in the pathogenesis of HF.
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PMID:Cardiopulmonary alterations in mRNA expression for interleukin-1beta, the interleukin-6 superfamily and CXC-chemokines during development of postischaemic heart failure in the rat. 1295 Mar 23

A comparative randomized clinical study was conducted to evaluate the diagnostic and prognostic value of the activation of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1alpha, IL-2, IL-6, IL-8)] and the increased production of autoimmune complexes in the pathogenesis of chronic heart failure (CHF) in patients with coronary heart disease (CHD). The study included 47 patients with CHD who had a more than 6-month history of Q-forming myocardial infarction. The patients were randomized into 3 groups: 1) 21 patients with NYHA Functional Class (FC) II heart failure (HF); 2) 16 patients with FC III HF; and 3) 10 with FC IV HF. Basic therapy involved angiotensin-converting enzyme (ACE) inhibitors, nitrates, diuretics, beta-adrenoblockers; 27.6% received digoxin, disaggregatory agents. A study protocol involved the estimation of the parameters of EchCG, paired bicycle ergometric tests, 6-min walking test, ECG daily monitoring, the levels of proinflammatory cytokines in the serum and IgG autoantibodies to cardiolipin. The findings suggest that with the higher expression of autoimmune complexes, the activation of cytokines (primarily TNF-alpha, IL-1alpha, IL-2) plays an important role in the pathogenesis of CHF in patients with postinfarct cardiac dysfunction: the high activation of cytokines and the elevated level of autoimmune complexes are associated with moderate or severe NYHA FC II-IV HF, depressed left ventricular contractility (ejection fraction, 23-38%), low exercise tolerance, and cardiac remodeling.
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PMID:[A role of activation of proinflammatory cytokines and production of autoimmune complexes in the pathogenesis of chronic heart failure in patients with postinfarct cardiac dysfunction]. 1546 17

The immune system of higher vertebrates consists of two components: the innate and adaptive immunity. While the adaptive immune system relies on somatically generated and clonally selected antigen receptors, the innate immune system detects the presence of pathogens by their evolutionarily highly conserved, relatively invariant structural motifs. Interestingly, recent data suggest that activation of the innate immune system could play an important role in various diseases without the direct involvement of infectious pathogens. For example, a number of inflammatory cytokines, including TNF (tumor necrosis factor), IL (interleukin)-1beta, IL-6 and IL-8, as well as iNOS (inducible nitric oxide synthase), all components of innate immunity, are also implicated in ischemia/reperfusion injury, and in the abnormal myocardial remodeling characteristic of chronic heart failure. Understanding of the regulation and activation of the innate immune system in diseases not obviously related to an immune response to specific pathogen could provide new therapeutic targets for cardiovascular diseases. Thus, in this review, we provide a general overview of the components of innate immunity with a focus on humoral factors, their role in the response to foreign pathogens, and their potential role in the response to tissue injury (i.e., the "Expanded Self-Non-Self" and the "Danger" theories of immune activation).
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PMID:Innate immunity and the heart. 1585 84

Peripheral monocytosis may affect the development of heart failure (HF) after acute myocardial infarction (AMI). Activated toll-like receptor (TLR) 4 in monocytes plays an important role in the synthesis of proinflammatory cytokines. We examined TLR4 expression in monocytes, which may be a possible source of proinflammatory cytokines in AMI. Sixty-five patients with AMI and 20 healthy subjects (HS) were studied. Monocytes were isolated from peripheral blood on days 1 and 14 after the onset of AMI. TLR4 levels in monocytes were measured using real-time RT-PCR and flow cytometry. Generation capacity was evaluated by TLR4 levels and cytokine concentrations in the culture medium with lipopolysaccharide (LPS) stimulation. On day 1 after onset, baseline levels of TLR4 and plasma proinflammatory cytokines, notably IL-6 and TNF-alpha, were higher in AMI patients than in HS. These levels remained elevated in AMI patients 14 days after onset. Generation capacities of TLR4 and proinflammatory cytokines (IL-2, IL-6, IL-8, IL-10, GM-CSF and TNF-alpha) were increased in AMI patients compared to HS. LPS-stimulated TLR4 levels were positively correlated with IL-6 and TNF-alpha levels in AMI patients. Baseline TLR4 levels and plasma proinflammatory cytokine (IL-6, GM-CSF and TNF-alpha) levels were higher in AMI patients with HF (n = 22) than in those without HF. Generation capacities of TLR4 and proinflammatory cytokines (IL-6, GM-CSF and TNF-alpha) were greater in AMI patients with HF than in those without HF. Activation of TLR4 through a myocytic inflammatory reaction is associated with HF after AMI. These observations suggest that TLR4 signaling in monocytes may play a role in the development of HF after AMI.
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PMID:Activated toll-like receptor 4 in monocytes is associated with heart failure after acute myocardial infarction. 1605 84

Elevated circulating levels of alpha- and beta-chemokines in heart failure have been reported. The objective of this study was to investigate the interrelation of chemotactic activity of serum and circulating chemokine levels in patients suffering from idiopathic dilated cardiomyopathy (IDCM). Chemokine serum levels (MCP-1, MIP1-alpha, RANTES, IL-8 and TNF-alpha) were determined in patients with IDCM (n = 10), patients with coronary artery disease with normal (CAD-1; n = 10) or depressed (CAD-2; n = 10) left ventricular function and healthy controls (n = 10). The chemotactic effect of sera obtained from these groups was measured using an in vitro chemotaxis assay. Sera obtained from IDCM (5475 +/- 681 cells) showed the highest chemotactic activity when compared to controls (1850 +/- 215 cells), CAD-1 (3325 +/- 275 cells) and CAD-2 (2800 +/- 275 cells, P < 0.05) associated with significantly higher circulating MCP-1 levels. Sera obtained from IDCM patients show a high chemotactic activity associated with significantly elevated circulating MCP-1.
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PMID:Chemotactic activity of serum obtained from patients with idiopathic dilated cardiomyopathy. 1696 15


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