Abstract
Objectives
This study sought to determine the circulating levels of cytokines and their respective endogenous modulators in patients with congestive heart failure of variable severity.Background
Activation of immune elements localized in the heart or periphery, or both, may promote release of cytokines in patients with congestive heart failure. Although an increased circulating level of tumor necrosis factor-alpha (TNF-alpha) and its soluble receptor type II (sTNF-RII) is well documented, less is known about other cytokines (i.e., interleukin-1-beta [IL-1-beta], interleukin-6 [IL-6] and interleukin-2 [IL-2] and their soluble receptor/receptor antagonists).Methods
Circulating levels of TNF-alpha and sTNF-RII, IL-1-beta, IL-1 receptor antagonist (IL-1-Ra), IL-6, IL-6 soluble receptor (IL-6-sR), IL-2 and IL-2 soluble receptor-alpha were measured using enzyme-linked immunosorbent assay kits (Quantikine, R&D Systems) in 80 patients with congestive heart failure due to coronary artery disease or hypertension. The severity of their symptoms, which ranged from New York Heart Association functional class I to IV, was confirmed by measurement of peak oxygen consumption.Results
The percentage of patients with elevated levels of cytokines and their corresponding soluble receptor/receptor antagonists significantly increased with functional class. For TNF-alpha and IL-1-beta, the percentage of patients with elevated levels of soluble receptor/receptor antagonists was higher than that of patients with elevated levels of the cytokine itself. For IL-6, the percentage of patients with elevated levels of IL-6-sR tended to be lower than that of patients with elevated levels of IL-6. All but two patients had undetectable levels of IL-2, and all but seven had levels of IL-2-sR within a normal range.Conclusions
In patients with congestive heart failure, circulating levels of cytokines increased with the severity of symptoms. In these patients, circulating levels of sTNF-RII and IL-1-Ra are more sensitive markers of immune activation than are circulating levels of TNF-alpha and IL-1-beta, respectively. Levels of IL-2 and IL-2-sR are not elevated when congestive heart failure is due to coronary artery disease or hypertension.References
Articles referenced by this article (22)
Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 1990;323:236–41.
McMurray J, Abdullah I, Dargie HJ, Shapiro D. Increased concentrations of tumor necrosis in cachetic patients with severe chronic heart failure. Br Heart J 1991;66:356–8.
Dutka DP, Elborn JS, Delamere F, Shale DJ, Morris GK. Tumour necrosis factor α in severe congestive cardiac failure. Br Heart J 1993;70:141–3.
Wiedermann CJ, Beimpold H, Herold M, Knapp E, Braunsteiner H. Increased levels of serum neopterin and decreased production of neutrophil superoxide anions in chronic heart failure with elevated levels of tumor necrosis factor-alpha. J Am Coll Cardiol 1993;22:1987–90.
Packer M. Is tumor necrosis factor an important neurohormonal mechanism in chronic heart failure? Circulation 1995;92:1379–82.
Matsumori A, Yamada T, Suzuki H, Matoba Y, Sasayama S. Increased circulating cytokines in patients with myocarditis and cardiomyopathy. Br Heart J 1994;72:561–6.
Katz SD, Rao R, Berman JW, et al. Pathophysiological correlates of increased serum tumor necrosis factor in patients with congestive heart failure: relation to nitric oxide-dependent vasodilation in the forearm circulation. Circulation 1994;90:12–6.
Limas CJ, Golderberg IF, Limas C. Soluble interleukin-2 receptor levels in patients with dilated cardiomyopathy: correlation with disease severity and cardiac autoantibodies. Circulation 1995;91:631–4.
Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, Mann DL. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol 1996;27:1201–6.
Ferrari R, Bachetti T, Confortini R, et al. Tumor necrosis factor soluble receptors in patients with various degrees of congestive heart failure. Circulation 1995;92:1479–86.
Show 10 more references (10 of 22)
Citations & impact
Impact metrics
Article citations
Effect of inferior caval valve implantation on circulating immune cells and inflammatory mediators in severe tricuspid regurgitation.
BMC Cardiovasc Disord, 24(1):373, 18 Jul 2024
Cited by: 0 articles | PMID: 39026154 | PMCID: PMC11256587
Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets.
Signal Transduct Target Ther, 9(1):130, 31 May 2024
Cited by: 5 articles | PMID: 38816371 | PMCID: PMC11139930
Review Free full text in Europe PMC
Interleukin-1 Inhibition for the Prevention and Treatment of Heart Failure.
J Cardiovasc Pharmacol, 83(6):522-530, 01 Jun 2024
Cited by: 1 article | PMID: 37815298
Review
Inflammation in heart failure: pathophysiology and therapeutic strategies.
Inflamm Res, 73(5):709-723, 28 Mar 2024
Cited by: 2 articles | PMID: 38546848 | PMCID: PMC11058911
Review Free full text in Europe PMC
The Role of Pro-Inflammatory Cytokines in the Pathogenesis of Cardiovascular Disease.
Int J Mol Sci, 25(2):1082, 16 Jan 2024
Cited by: 26 articles | PMID: 38256155 | PMCID: PMC10817020
Review Free full text in Europe PMC
Go to all (314) article citations
Similar Articles
To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.
Soluble tumor necrosis factor receptors are elevated in relation to severity of congestive heart failure.
Jpn Circ J, 61(8):657-664, 01 Aug 1997
Cited by: 42 articles | PMID: 9276770
Circulating levels of cytokines and their site of production in patients with mild to severe chronic heart failure.
Am Heart J, 140(6):E28, 01 Dec 2000
Cited by: 40 articles | PMID: 11100001
Cytokine inhibitors in patients with heart failure and impaired functional capacity.
Jpn Circ J, 61(9):749-754, 01 Sep 1997
Cited by: 6 articles | PMID: 9293404
[Cytokines--causes, players or bystanders in heart failure].
Herz, 27(7):691-698, 01 Nov 2002
Cited by: 3 articles | PMID: 12439641
Review