Cited by 2,582Heart Failure Treatment and ManagementCardiac Fibrosis and RemodelingNutrition and Health in Aging

The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.

Elevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure

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Levine, Beth, Kalman, Jill, Mayer, Lloyd, Fillit, Howard M., Packer, Milton·1990·New England Journal of Medicine

DOI 10.1056/nejm199007263230405

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Abstract

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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“[13] Levine B, Kalman J, Mayer L, Fillit HM, Packer M.”
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Background
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BackgroundResult
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Background
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Background
Haemodynamic, neuroendocrine and metabolic correlates of circulating cytokine concentrations in congestive heart failure
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“In HF patients, inflammatory activity is increased (22), and it is tempting to suggest that like GDF15, HE4 may have an immunomodulatory function.”
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Cappuzzello, C., Vito, L. D., Melchionna, R., Melillo, G., Silvestri, L., Cesareo, E., Crea, F., Liuzzo, G., Facchiano, A., Capogrossi, M. C., et al. (2011) · Journal of Translational Medicine · doi:10.1186/1479-5876-9-28 · Cited by 74
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BackgroundInfluential
IRAK1 deletion disrupts cardiac Toll/IL-1 signaling and protects against contractile dysfunction
Thomas, J. A., Haudek, S. B., Köroğlu, T., Tsen, M. F., Bryant, D. D., White, D. J., Kusewitt, D. F., Horton, J. W., & Giroir, B. P. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.0655.2001 · Cited by 74
“proinflammatory cytokine concentrations (18, 27), which may be both markers for worsening cardiac function and stimuli contributing to further deterioration in contractility.”
Background
Circulating levels of cytokines and their site of production in patients with mild to severe chronic heart failure
Petretta, M., Condorelli, G., Spinelli, L., Scopacasa, F., Caterina, M. D., Leosco, D., Vicario, M. L. E., & Bonaduce, D. (2000) · American Heart Journal · doi:10.1067/mhj.2000.110935 · Cited by 74
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Arachidonic acid mediates dual effect of TNF-α on Ca2+ transients and contraction of adult rat cardiomyocytes
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Background
The Search for the Ideal Positive Inotropic Agent
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Self-citation
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ESPEN Guidelines on Parenteral Nutrition: On Cardiology and Pneumology
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Background
Cytokine mediation of experimental heart failure-induced anhedonia
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“Serum levels of TNF- are increased in humans with heart failure associated with ischemic heart disease (24) and in rats with experimental heart failure (16).”
Background
Interleukin-10 Improves Left Ventricular Function in Rats with Heart Failure Subsequent to Myocardial Infarction
Stumpf, C., Seybold, K., Petzi, S., Wasmeier, G. H., Raaz, D., Yılmaz, A., Anger, T., Daniel, W. G., & Garlichs, C. D. (2008) · European Journal of Heart Failure · doi:10.1016/j.ejheart.2008.06.007 · Cited by 73
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The cardiopulmonary continuum systemic inflammation as ‘common soil’ of heart and lung disease
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Insulin resistance in moderate chronic heart failure is related to hyperleptinaemia, but not to norepinephrine or TNF-alpha
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Managing Immunogenic Responses to Infliximab
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The Clinical Relevance of Circulating Tumor Necrosis Factor-α in Acute Decompensated Chronic Heart Failure Without Cachexia
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Recent Insights into the Role of Tumor Necrosis Factor in the Failing Heart
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“In an effort to define a biochemical mechanism for cardiac cachexia, Levine et al. made the sentinel observation that patients with advanced heart failure (NYHA class III‐IV) expressed elevated levels of biologically active TNF in their peripheral circulation [ 35 ].”
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Proteins and Phospholipids in BAL From Patients With Hydrostatic Pulmonary Edema
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How are Cytokines Activated in Heart Failure?
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“In HF, weight loss and inflammatory cytokine activation are linked, and are associated with increased mortality (8,9,53).”
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Prediction of Mortality by High-Sensitivity C-Reactive Protein and Brain Natriuretic Peptide in Patients With Dilated Cardiomyopathy
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Ambient Temperature and Biomarkers of Heart Failure: A Repeated Measures Analysis
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Inflammatory Biomarkers in Heart Failure
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“Cardiac cachexia, which is a catabolic state characterized by weight loss and muscle wasting, occurs frequently in patients with end-stage CHF (14-16) and is a strong independent risk factor for mortality in patients with CHF (18).”
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Prognostic value of plasma chromogranin A levels in patients with complicated myocardial infarction
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New insights into the pathological role of TNF-α in early cardiac dysfunction and subsequent heart failure after infarction in rats
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Erythropoiesis-stimulating agents for anaemia in chronic heart failure patients
Ngo, K., Kotecha, D., Walters, J. A., Manzano, L., Palazzuoli, A., van Veldhuisen, D. J., & Flather, M. D. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007613.pub2 · Cited by 72
Novel Concept of a Heart-Gut Axis in the Pathophysiology of Heart Failure
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Elevated plasma levels of tumor necrosis factor in chronic heart failure with cachexia
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Estrogen is associated with improved survival in aging women with congestive heart failure: analysis of the vesnarinone studies
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N -Acetylcysteine Prevents the Deleterious Effect of Tumor Necrosis Factor-α on Calcium Transients and Contraction in Adult Rat Cardiomyocytes
Cailleret, M., Amadou, A. S., Andrieu‐Abadie, N., Nawrocki, A., Adamy, C., Aït-Mamar, B., Rocaries, F., Best‐Belpomme, M., Levade, T., Pavoine, C., et al. (2004) · Circulation · doi:10.1161/01.cir.0000109499.00587.ff · Cited by 71
“Taken together, these data support the proposal that the effects of NAC in vivo treatment described here (1) are caused by the conversion of NAC into glutathione and are not imputable to a NAC byproduct and (2) are linked to an increase in”
Background
Nitric Oxide Modulates Myocardial Oxygen Consumption in the Failing Heart
Chen, Y., Traverse, J. H., Du, R., Hou, M., & Bache, R. J. (2002) · Circulation · doi:10.1161/01.cir.0000021120.90970.b9 · Cited by 71
Evidence for Inflammation as a Cause of Hypocholesterolemia in Older People
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Background
Leptin serum levels in cachectic heart failure patients
Filippatos, G. S., Tsilias, K. P., Venetsanou, K. F., Karambinos, E., Manolatos, D., KRANIDIS, A. J., Antonellis, J. P., Kardaras, F. G., Anthopoulos, L. P., & Baltopoulos, G. J. (2000) · International Journal of Cardiology · doi:10.1016/s0167-5273(00)00397-1 · Cited by 70
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“c ollowing reports that serum tumor necrosis factor (TNF)lpha concentrations are elevated in patients with severe hronic heart failure (CHF) (1), an appreciable research ffort has attempted to describe the role of the immune ystem in the disease.”
Background
Prognostic value of pentraxin 3 in patients with chronic heart failure
Kotooka, N., Inoue, T., Aoki, S., Anan, M., Komoda, H., & Node, K. (2007) · International Journal of Cardiology · doi:10.1016/j.ijcard.2007.07.168 · Cited by 70
Neurohormonal Activation in Acute Heart Failure: Results from VERITAS
Milo‐Cotter, O., Davison, B. A., Lombardi, C., Sun, H., Bettari, L., Bugatti, S., Rund, M. M., Metra, M., Kaluski, E., Kobrin, I., et al. (2011) · Cardiology · doi:10.1159/000330409 · Cited by 70
“The growing evidence that inflammation plays a pivotal role in the pathogenesis of heart failure has led to the use of inflammatory mediators as markers of risk in heart failure. As consistent data accumulate in this field, risk prediction for patients with ischemic heart disease and heart failure in particular repres…”
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P1 receptors and cytokine secretion
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“inflammatory cytokines in patients with heart failure in 1990 [70], there has been a growing interest in understand-”
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High plasma level of asymmetric dimethylarginine in patients with acutely exacerbated congestive heart failure: role in reduction of plasma nitric oxide level
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BackgroundMethod
A novel chronoamperometric immunosensor for rapid detection of TNF-α in human saliva
Barhoumi, L., Baraket, A., Bellagambi, F. G., Karanasiou, G. S., Ali, M. B., Fotiadis, D. I., Bausells, J., Zine, N., Sigaud, M., & Errachid, A. (2018) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2018.03.135 · Cited by 70
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Authors: Levine, B., Kalman, J., Mayer, L., Fillit, H. M., & Packer, M.
Affiliations: City University of New York (US)
ORCID: Levine, Beth
Fillit, Howard M.
Packer, Milton
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
DOI: 10.1056/nejm199007263230405
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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Elevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure

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