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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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Neurohormonal factors in the development of catabolic/anabolic imbalance and cachexia
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Tumor necrosis factor-α and the failing human heart-TNFα and heart failure
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“The link between HF and inflammation was first recognized in 1990 by Levine [26].”
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“…of inflammatory cytokines is increased, such as interleukin-6 and tumour necrosis factor alpha, which are associated with the severity of HF. 59,60 Activated platelets expressing P-selectin and CD40 ligand form aggregates with monocytes and promote the inflammatory process and initiate…”
BackgroundCardiac biomarkers in heart failure
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Can Vaccinations Improve Heart Failure Outcomes?
Bhatt, A. S., DeVore, A. D., Hernandez, A. F., & Mentz, R. J. (2017) · JACC Heart Failure · doi:10.1016/j.jchf.2016.12.007 · Cited by 60
Novel applications for serum procalcitonin testing in clinical practice
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“High cortisol levels [4,24], stimulation of beta-adrenergic receptor in the lymphocytes due to increased sympathetic tone [22], and elevated cytokines [25] have all shown to cause lymphopenia.”
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“Proinflammatory cytokine tumor necrosis factor-a (TNF-a), has been shown to have a cardiodepressent effect and is involved in various cardiovascular complications [1,2].”
BackgroundIron Regulatory Hormone Hepcidin Decreases in Chronic Heart Failure Patients With Anemia
Matsumoto, M., Tsujino, T., Lee‐Kawabata, M., Naito, Y., Akahori, H., Sakoda, T., Ohyanagi, M., Tomosugi, N., & Masuyama, T. (2010) · Circulation Journal · doi:10.1253/circj.cj-09-0663 · Cited by 59
Cardiac Intercellular Communication: Are Myocytes and Fibroblasts Fair-Weather Friends?
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“human HF patients have been observed in a manner corresponding to functional class [96, 97], suggesting correlation with disease pathophysiology.”
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“Following reports that serum tumor necrosis factor (TNF) concentrations were elevated in patients with CHF [1], considerable effort has been made to describe the role of the immune system in this disease.”
BackgroundHeart failure risk among patients with rheumatoid arthritis starting a TNF antagonist
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Early Inflammatory Response During the Development of Right Ventricular Heart Failure in a Rat Model
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ERBB signaling attenuates proinflammatory activation of nonclassical monocytes
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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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