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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines are being increasingly recognized as important factors in the pathogenesis and pathophysiology of heart failure. Elevated levels of circulating cytokines have been reported in patients with heart failure, and various cytokines have been shown to depress myocardial contractility in vitro and in vivo. Our recent study showed that the various drugs for heart failure modulated the production of cytokines, and some of these drugs inhibited activation of NF-kappa B. Cytokine gene therapy which inhibits inflammatory response by viral IL-10 and IL-1 receptor antagonist has been shown to be effective in the animal models of heart failure. Mast cells have been shown to play important role in the pathogenesis of heart failure due to viral myocarditis, and transition from compensated hypertrophy to heart failure.
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PMID:[Roles of cytokines in the pathogenesis of heart failure]. 1275 97

Current therapies for the treatment of myocardial infarction and heart failure include medical, surgical, mechanical assist, and transplantation. These therapies have been based on the dogma that ventricular myocytes themselves are terminally differentiated and, therefore, cannot regenerate. This concept has been recently challenged with stem cell therapy. A potential problem is the ability of cardiac tissue to mobilize, recruit, and transdifferentiate adult stem cells from other tissues. We believe that there is a unique failure of the damaged myocardium to provide the appropriate molecular signals for stem cells engraftment related to age. Our hypothesis is that the overexpression of IL-10 in the aged population reduces cardiac cellular proliferation subsequent to myocardial injury. This hypothesis is supported by aging models, where elevated levels of IL-10 are associated with reduced healing response to noncardiac tissue injury. We demonstrated an increased cardiac gene expression of IL-10 that may be associated with a reduced proliferative response in the border regions of the infarcted myocardium that are proportional with age. In conclusion, myocardial infarction and heart failure has presented a significant challenge for the clinician to provide reparative therapies. The use of therapeutics to modulate IL-10 and, thereby, optimizing regenerative processes in the injured myocardium may provide a unique means for the cardiac patient.
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PMID:Relationship of aging and cardiac IL-10. 1533 66

Recent studies point to important interactions between proinflammatory cytokines and neurohumoral mediators in heart failure. Here we investigate the influence of the beta-adrenergic system on cytokines and neurohumoral factors and the sequelae of viral myocarditis. In an experimental model with virus-infected BALB/c mice, we studied the acute and chronic effects of epinephrine and propranolol on myocardial morphology, cytokine gene expression, and survival. BALB/c mice were inoculated with the encephalomyocarditis virus (EMCV) or sham inoculated with saline and followed for 30 days. Epinephrine increased the severity of inflammatory cell infiltration and myocardial necrosis induced by EMCV. Gene expression of TNF-alpha, IL-6, and IL-10 was markedly enhanced by epinephrine in EMCV-inoculated mice. Survival rate after 30 days was reduced to 40% in epinephrine-treated EMCV-inoculated mice compared with 70% in untreated EMCV-inoculated mice (P < 0.05). Treatment with the beta-blocker propranolol significantly decreased mortality, myocardial necrosis, and infiltration of inflammatory cells in EMCV-inoculated mice. Propranolol also suppressed gene expression of TNF-alpha, IL-6, and IL-10. A single dose of epinephrine 120 days after EMCV inoculation caused sudden death in 70% of infected mice; propranolol significantly reduced incidence of death to 33%. These results indicate that acute and chronic stages of viral myocarditis are modulated by the beta-adrenergic system and its interactions with proinflammatory cytokines.
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PMID:Propranolol ameliorates and epinephrine exacerbates progression of acute and chronic viral myocarditis. 1592 19

Accumulating evidence indicates that inflammatory mediators are important in the pathogenesis of chronic heart failure (CHF), contributing to cardiac remodeling and peripheral vascular disturbances. Several studies have shown increased levels of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 in patients with CHF in both plasma and circulating leukocytes as well as in the failing myocardium itself. Importantly, this increase in inflammatory mediators does not seem to be accompanied by a corresponding increase in anti-inflammatory cytokines, such as IL-10 and transforming growth factor-beta, resulting in an inflammatory imbalance in the cytokine network. Traditional cardiovascular drugs seem to have little influence on the cytokine network in patients with CHF, and immunomodulatory therapy in addition to "optimal" cardiovascular treatment regimens has emerged as an option. Thus, several animal studies as well as some clinical pilot trials have suggested that downregulation of inflammatory cytokines may improve cardiac performance. On the other hand, preliminary results from placebo-controlled anti-TNF studies suggest no effect, or even an adverse effect of anti-TNF therapy on mortality and hospitalization. Although somewhat disappointing, these negative results do not necessarily argue against the cytokine hypothesis. These studies only underscore the difficulties and challenges in developing treatment modalities that can modulate the cytokine network in patients with CHF, resulting in anti-inflammatory and beneficial net effects. Further research in this area will have to more precisely identify the most important "actors" in the immunopathogenesis of CHF to improve the immunomodulatory treatment regimens in this disorder.
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PMID:Review of trials in chronic heart failure showing broad-spectrum anti-inflammatory approaches. 1592 60

The immune system is a system of dynamic equilibrium, with inflammatory responses (mediated by T helper type 1 cells, interleukin [IL]-1beta, interferon-gamma, and tumor necrosis factor-alpha [TNF-alpha]) being balanced by anti-inflammatory responses (mediated by T regulatory type 1 cell, T helper type 3 cells, IL-4, IL-10, and transforming growth factor-beta). Therefore, neutralization of inappropriate inflammatory cytokines is a therapeutic strategy that has been attempted in many chronic inflammatory conditions, mostly targeting TNF-alpha, using either monoclonal antibodies or modified receptor proteins (etanercept). There is functional redundancy among the inflammatory cytokines. For example, in addition to TNF-alpha, both IL-1beta and IL-6 are elevated in patients with chronic heart failure (CHF); thus neutralizing the activity of TNF-alpha alone may be an inadequate approach in this patient group. Immune-modulation therapy (IMT) results in downregulation of proinflammatory cytokine levels and upregulation of anti-inflammatory cytokines. This alteration in the balance between proinflammatory and anti-inflammatory cytokines may be more appropriate than neutralizing the activity of a single cytokine in the treatment of conditions such as CHF. Several animal studies investigating the effect of IMT in inflammatory conditions including allergic contact hypersensitivity, ischemia reperfusion injury, and atherogenesis are reviewed.
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PMID:Biologic effects and basic science of a novel immune-modulation therapy. 1592 61

Evidence from both experimental and clinical trials indicates that inflammatory mediators are important in the pathogenesis of chronic heart failure (HF), contributing to cardiac remodelling and peripheral vascular disturbances. Several studies have shown raised levels of inflammatory cytokines such as TNF-alpha, IL-1beta and -6 in HF patients in plasma, circulating leukocytes, atherosclerotic lesions, and in the failing myocardium itself. Importantly, this rise in inflammatory mediators does not seem to be accompanied by a corresponding increase in anti-inflammatory cytokines such as IL-10 and transforming growth factor-beta; thus resulting in an inflammatory imbalance in the cytokine network. Traditional cardiovascular drugs have little influence on the cytokine network in HF patients. Results from randomised, placebo-controlled anti-TNF studies suggest lack of effect of such therapy. Although somewhat disappointing, these negative results do not necessarily argue against the 'cytokine hypothesis'; these studies just underscore the challenges in understanding the complex cytokine network in order to develop effective treatment modalities in HF patients. More general immunmodulating treatments, such as pentoxyfylline, intravenous immunoglobulin, thalidomide and statins, have shown promising results in smaller studies, which need to be confirmed in larger studies with hospitalisations and death as the end points. In addition, further research in this area will have to be more precise in identifying the most important 'actors' in the immunopathogenesis of chronic HF.
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PMID:Agents targeting inflammation in heart failure. 1592 63

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

Endotoxic shock, one of the most prominent causes of mortality in intensive care units, is characterized by pulmonary hypertension, systemic hypotension, heart failure, widespread endothelial activation/injury, and clotting culminating in disseminated intravascular coagulation and multi-organ system failure. In the last few years, studies in rodents have shown that administration of low concentrations of carbon monoxide (CO) exerts potent therapeutic effects in a variety of diseases/disorders. In this study, we have administered CO (one our pretreatment at 250 ppm) in a clinically relevant, well-characterized model of LPS-induced acute lung injury in pigs. Pretreatment only with inhaled CO significantly ameliorated several of the acute pathological changes induced by endotoxic shock. In terms of lung physiology, CO pretreatment corrected the LPS-induced changes in resistance and compliance and improved the derangement in pulmonary gas exchange. In terms of coagulation and inflammation, CO reduced the development of disseminated intravascular coagulation and completely suppressed serum levels of the proinflammatory IL-1beta in response to LPS, while augmenting the anti-inflammatory cytokine IL-10. Moreover, the effects of CO blunted the deterioration of kidney and liver function, suggesting a beneficial effect in terms of end organ damage associated with endotoxic shock. Lastly, CO pretreatment prevents LPS-induced ICAM expression on lung endothelium and inhibits leukocyte marginalization on lung parenchyma.
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PMID:Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs. 1622 83

The expression of proinflammatory cytokines increases in hypothalamus of rats with myocardial infarction (MI) and heart failure. We used central gene transfer of human interleukin (IL)-10, a potent antiinflammatory cytokine, to counter the effects of brain proinflammatory cytokines and examine their functional significance. Sprague-Dawley rats underwent coronary ligation to induce MI or sham surgery (SHAM). One week later, adenoviral vectors encoding human IL-10 (AdIL-10) or beta-galactosidase (betaGal) were injected (30 microL over 30 minutes) into lateral ventricle. One week after injection, there was abundant expression of human IL-10 in the brain of MI+AdIL-10 and SHAM+AdIL-10 rats. Compared with SHAM+betaGal, MI+betaGal had increased (P<0.05) IL-1beta and cyclooxygenase-2 mRNA and protein and nuclear factor kappaB activity in the hypothalamus, cyclooxygenase-2 fluorescence in perivascular cells of the paraventricular nucleus of hypothalamus, prostaglandin E(2) in cerebrospinal fluid, and Fra-like activity (indicating neuronal excitation) in paraventricular nucleus. Plasma norepinephrine levels, lung/body weight, right ventricle/body weight, and left ventricular end-diastolic pressure were increased and maximal left ventricular dP/dt was decreased. All of these findings were ameliorated in MI rats treated with AdIL-10. Hypothalamic tumor necrosis factor-alpha and circulating tumor necrosis factor-alpha and IL-1beta levels, also increased in MI+betaGal, were not affected by AdIL-10 treatment. Rat native IL-10 was not affected by MI or AdIL-10. AdIL-10 had no effects on SHAM rats. The results demonstrate that cardiovascular and autonomic mechanisms leading to heart failure after MI can be modulated by manipulating the balance between proinflammatory and antiinflammatory cytokines in the brain.
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PMID:Central gene transfer of interleukin-10 reduces hypothalamic inflammation and evidence of heart failure in rats after myocardial infarction. 1767 79

Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF-alpha occur and contribute to the development of cardiac dysfunction and subsequent heart failure. The aim of the present study was to determine whether similar phenomena also occur after ischemia-reperfusion and whether cytokines other than TNF-alpha can also be involved. Anesthetized male Wistar rats were subjected to 1 h coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5, 7, 8, and 10 postligation. Before death, heart function was assessed in vivo under basal conditions, as well as after volume overload. Finally, hearts were frozen for histoenzymologic assessment of infarct size and remodeling. The profile of cardiac cytokines was determined by ELISA and ChemiArray on heart tissue extracts. As expected, ischemia-reperfusion induced a progressive remodeling of the heart, characterized by left ventricular free-wall thinning and cavity dilation. Heart function was also decreased in ischemic rats during the first week after surgery. Interestingly, a transient and marked increase in TNF-alpha, IL-1beta, IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3alpha was also observed in the myocardium of myocardial ischemia (MI) animals at day 8, whereas the expression of anti-inflammatory interleukins IL-4 and IL-10 remained unchanged. These results suggest that overexpression of proinflammatory cytokines occurring during the first week after ischemia-reperfusion may play a role in the adaptative process in the myocardium and contribute to early dysfunction and remodeling.
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PMID:Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling. 1787 14


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