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Elevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure
Open accessAbstract
BACKGROUND AND METHODS: Although cachexia often accompanies advanced heart failure, little is known about the causes of the cachectic state. To assess the potential role of tumor necrosis factor in the pathogenesis of cardiac cachexia, we measured serum levels of the factor in 33 patients with chronic heart failure, 33 age-matched healthy controls, and 9 patients with chronic renal failure. RESULTS: Mean (+/- SEM) serum levels of tumor necrosis factor were higher in the patients with heart failure (115 +/- 25 U per milliliter) than in the healthy controls (9 +/- 3 U per milliliter; P less than 0.001). Nineteen of the patients with chronic heart failure had serum levels of tumor necrosis factor greater than or equal to 39 U per milliliter (greater than 2 SD above the mean value for the control group), whereas the remaining 14 patients had serum levels of tumor necrosis factor below this level. The patients with high levels of tumor necrosis factor were more cachectic than those with low levels (82 +/- 3 vs. 95 +/- 6 percent of ideal body weight, respectively; P less than 0.05) and had more advanced heart failure, as evidenced by their higher values for plasma renin activity (2.92 +/- 0.53 vs. 1.06 +/- 0.53 ng per liter per second [10.5 +/- 1.9 vs. 3.8 +/- 1.9 ng per milliliter per hour]; P less than 0.01) and lower serum sodium concentration (135 +/- 1 vs. 138 +/- 1 mmol per liter; P less than 0.05). The group with high levels of tumor necrosis factor also had lower hemoglobin levels (7.82 +/- 0.2 vs. 8.69 +/- 0.4 mmol per liter [12.6 +/- 0.4 vs. 14.0 +/- 0.6 g per deciliter]) and higher values for blood urea nitrogen (19.5 +/- 2.2 vs. 12.5 +/- 1.8 mmol per liter) than the group with low levels of tumor necrosis factor (P less than 0.05 for both). The high levels of tumor necrosis factor were not due solely to decreased renal clearance, however, since the levels in the patients with heart failure were considerably higher than those in the nine patients with chronic renal failure (115 +/- 25 vs. 45 +/- 25 U per milliliter; P less than 0.05). CONCLUSIONS: These findings indicate that circulating levels of tumor necrosis factor are increased in cachectic patients with chronic heart failure and that this elevation is associated with the marked activation of the renin-angiotensin system seen in patients with end-stage cardiac disease.
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“in patients with congestive heart failure, the levels of pro-inflammatory cytokines, especially TNF, IL-6, and IL-1, are markedly elevated, and the TNF level is a negative prognostic factor”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [191]
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Sliwa, K. S., Woodiwiss, A. J., Candy, G. P., Badenhorst, D., Libhaber, C. D., Norton, G. R., Skudicky, D., & Sareli, P. (2002) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)02779-0 · Cited by 106
Structural, functional, and molecular characterization of the SHHF model of heart failure
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The pulmonary cachexia syndrome: aspects of energy balance
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Cytokines and Cardiomyocyte Death
Pulkki, K. J. (1997) · Annals of Medicine · doi:10.3109/07853899708999358 · Cited by 106
Inflammatory Biomarkers in Heart Failure Revisited: Much More than Innocent Bystanders
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Interferon-γ Induces Chronic Active Myocarditis and Cardiomyopathy in Transgenic Mice
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Daily energy expenditure in free-living heart failure patients
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Cellular Basis for the Acute Inhibitory Effects of IL-6 and TNF- on Excitation-contraction Coupling
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Effects of Tumor Necrosis Factor Gene Polymorphisms on Patients With Congestive Heart Failure
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Free radicals, cytokines and nitric oxide in cardiac failure and myocardial infarction
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Increased Superoxide in Heart Failure
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“In patients with chronic HF [7,37] and in animal models of chronic left-ventricular dysfunction [10,63], reduced skeletal muscle expression of IGF-I is associated with muscle atrophy.”
BackgroundProinflammatory cytokines in acute myocardial infarction with and without cardiogenic shock
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“Elevated TNF-a levels were found repeatedly in patients with advanced congestive heart failure [15, 20 , 29].”
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“Introduction the progression and symptoms of CHF [5,6], i.”
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Role of cytokines in heart failure
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Targeted Anticytokine Therapy and the Failing Heart
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Enhanced generation of interleukins 1 beta and 6 may contribute to the cachexia of chronic disease
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“Altered Body Composition and Inflammation: It has become increasingly evident that fat tissue is an active endocrine organ that may produce several adipokines, including proinflammatory substances such as IL-1, TNFα, and plasminogen activator inhibitor type 1 (93).”
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“For example, with heart failure there are systemic elevations of norepinephrine (10, 24), arginine vasopressin (24), endothelin (5, 14), and tumor necrosis factor (11).”
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“A role for TNF-a as a modulator of cardiac function has been proposed and substantiated by the relative spatial and temporal expression of this cytokine in the myocardium but notably by its upregulation during mechanical load (47) in surviving myocytes after infarction (35) and end-stage heart failure (31, 48).”
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Metadata
- Authors
- Levine, B., Kalman, J., Mayer, L., Fillit, H. M., & Packer, M.
- Affiliations
- City University of New York (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1990-07-26
- Volume
- 323
- Issue
- 4
- Pages
- 236-241
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2324476825
- Cited by
- 2,582
- References
- 55
- Citations by year
- 2026: 21 · 2025: 43 · 2024: 49 · 2023: 34 · 2022: 70 · 2021: 63 · 2020: 64 · 2019: 64 · 2018: 59 · 2017: 64 · 2016: 58 · 2015: 70 · 2014: 75 · 2013: 73 · 2012: 79
- FWCI
- 29.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7r01hl025055-11, 5r01ca041583-06, 5k04hl001229-02)
- National Heart, Lung, and Blood Institute (KO4-HL-01229, R01-HL-25055)
- National Cancer Institute (R01-CA41583)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Keywords
- TNF-α, chronic heart failure, cardiac cachexia, serum cytokines, plasma renin activity, serum sodium, hemoglobin, blood urea nitrogen, chronic kidney disease, cytokine clearance, advanced heart failure, weight loss, inflammation in heart failure, anemia of heart failure, hyperuricemia, hyperkalemia
- MeSH terms
- Adult, Aged, Aged, 80 and over, Chronic Disease, Female, Heart Failure, Hemoglobins, Humans, Male, Middle Aged, Renin, Sodium, Tumor Necrosis Factor-alpha
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