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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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“production and release of autoantibodies, pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), and complement system recruitment (3-6).”
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“Advanced HF causes peripheral hypoperfusion, which leads to enhanced neurohormonal activation, oxidative stress, and systemic inflammatory activity.(30,31) These conditions would lead to insulin resistance, impaired protein and lipid metabolisms, anabolic deficiency, and anabolic-catabolic imbalance.”
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“Additionally, clinical studies have identified enhanced levels of circulating TNF‑ α , IL-1 β , IL-6 and other pro-inflammatory cytokines in patients with myocarditis (25,26).”
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BackgroundEnhanced activation of pro-inflammatory cytokines in mice lacking natriuretic peptide receptor-A
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“Furthermore, inappropriate activation of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) have been recognized as an important mediator in the development of endothelial dysfunction, cardiac hypertrophy, and heart failure in experimental animal models and in humans (9,17,28,3…”
BackgroundCytokine profile in chronic cardiac failure
Steele, I. C., Nugent, A. M., Maguire, S., Hoper, M., Campbell, G. R., Halliday, M., & Nicholls, D. (1996) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1996.2560587.x · Cited by 45
Increased Neutrophil Lifespan in Patients with Congestive Heart Failure
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Gender-related differences in myocardial inflammatory and contractile responses to major burn trauma
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“The role of inflammation in myocardial dysfunction has been further supported by the finding that patients with heart failure have increased circulating levels of IL-1 and TNF- , and the extent to which concentrations of these inflammatory mediators were elevated correlated with greater myocardial dysfunction (22, 43).”
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Skeletal Muscle Function, Morphology, and Metabolism in Patients with Congestive Heart Failure
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Mitral Valve Repair in Heart Failure
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Crisóstomo, V., Báez-Díaz, C., Maestre, J., García-Lindo, M., Sun, F., Casado, J. G., Blázquez, R., Abad, J. L., Palacios, I., Rodrı́guez-Borlado, L., et al. (2015) · Journal of Translational Medicine · doi:10.1186/s12967-015-0512-2 · Cited by 44
“myocardium [41] and has been extensively described in different animal models of cardiovascular failure [42].”
BackgroundHeart Failure-Induced Cachexia
Okoshi, M. P., Romeiro, F. G., de Paiva, S. A. R., & Okoshi, K. (2013) · Arquivos Brasileiros de Cardiologia · doi:10.5935/abc.20130060 · Cited by 44
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Recent insights on the molecular mechanisms and therapeutic approaches for cardiac cachexia
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Mechanisms for Cachexia in Heart Failure
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“Elevated levels of TNF are seen in CHF patients and it is strongly correlated with the NYHA scale [68].”
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“[35] reported that HF-related increases in serum TNF-α levels are associated with skeletal muscle wasting.”
BackgroundDifferential Effects of Amrinone and Milrinone Upon Myocardial Inflammatory Signaling
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Differential Effects of Chitooligosaccharides on Serum Cytokine Levels in Aged Subjects
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Anti‐Inflammatory Effect of Cardiac Resynchronization Therapy
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“03 ng/ml) from previous studies [3,4,16,17].”
Weight loss in chronic obstructive pulmonary disease
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The Emerging Field of Cardioimmunology: Past, Present and Foreseeable Future
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BackgroundA Review of Causes and Systemic Approach to Cardiac Troponin Elevation
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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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