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(Circulation. 1995;92:1479-1486.)
© 1995 American Heart Association, Inc.
Articles |
Tumor Necrosis Factor Soluble Receptors in Patients With Various Degrees of Congestive Heart Failure
From the Cattedra di Cardiologia, Università degli Studi di Brescia (R.F., R.C., O.V.); the Centro di Fisiopatologia Cardiovascolare "Salvatore Maugeri," Fondazione Clinica del Lavoro, Gussago, Brescia (T.B.); the Heart Failure Unit, Fondazione Clinica del Lavoro, Montescano, Pavia (C.O., O.F.); and Tecnogen ScpA, Piana di Monte Verna, Caserta (A.C., G.C.), Italy.
Correspondence to Prof Roberto Ferrari, Cattedra di Cardiologia, Università degli Studi di Brescia, c/o Spedali Civili, P.le Spedali Civili, 1, 25123 Brescia, Italy.
Background Tumor necrosis factor alpha (TNF-
)
increases in patients with severe congestive heart failure (CHF) and
cachexia. Two naturally occurring modulators of TNF- activity have
been identified in human serum. These two soluble proteins are the
extracellular domains of the TNF receptors (sTNF-RI and sTNF-RII,
respectively). The determination of circulating sTNF-Rs could provide
us with some additional information about the activation of this
cytokine in CHF.
Methods and Results This study was undertaken to examine the
concentration of sTNF-Rs and of bioactive and antigenic TNF- in 37
consecutive patients with various degrees of CHF compared with that of
26 age-matched healthy subjects. Antigenic TNF- increased (from
14.3±7.08 to 33.5±13.1 pg/mL, P<.001) in preterminal
patients with severe CHF (New York Heart Association [NYHA] class
IV). In these patients, sTNF-Rs were also increased (sTNF-RI from
1.17±0.43 to 4.43±2.14 ng/mL and sTNF-RII from 2.2±0.44
to
7.55±2.28 ng/mL, P<.001). When measured by cytolytic
bioassay, TNF- was undetectable (<100 pg/mL). Addition of 625 pg/mL
recombinant human TNF- (rhTNF-), corresponding in the bioassay to
60% of the lethal dose, to the serum of healthy subjects resulted in a
significant increase of the expected cytotoxicity (from 625 to
1290±411 pg/mL, P<.001). Addition of the same dose of
rhTNF- to the serum of patients with mild to moderate CHF (NYHA
classes II and III) increased the cytotoxicity from 625 to 877±132
pg/mL, P<.001. In 4 patients with severe CHF (class IV),
the expected cytotoxicity was completely inhibited, whereas it was
reduced from 625 to 263±198 pg/mL, P<.001, in the
remaining 8 patients. Ten patients died within 1 month of entry into
the study. They had the highest level of sTNF-RII (8.18±1.92 ng/mL).
sTNF-RII was a more powerful independent indicator of mortality than
TNF-, sTNF-RI, NYHA class, norepinephrine, and atrial
natriuretic peptide.
Conclusions Measurement of sTNF-Rs, in addition to antigenic and
bioactive TNF-, is essential for evaluation of the activation of
this cytokine in CHF. Both sTNF-Rs increase in preterminal
patients with severe CHF and might inhibit the in vitro cytotoxicity of
TNF-. Antigenic TNF- also increases in severe CHF. The increased
levels of sTNF-RII independently correlate with poor short-term
prognosis.
Key Words: hormones • proteins • heart failure • receptors
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S. R. Kapadia, K. Yakoob, S. Nader, J. D. Thomas, D. L. Mann, and B. P. Griffin Elevated circulating levels of serum tumor necrosis factor-alpha in patients with hemodynamically significant pressure and volume overload J. Am. Coll. Cardiol., July 1, 2000; 36(1): 208 - 212. [Abstract] [Full Text] [PDF]
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H. R Gosker, E. F. Wouters, G. J van der Vusse, and A. M. Schols Skeletal muscle dysfunction in chronic obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy perspectives Am. J. Clinical Nutrition, May 1, 2000; 71(5): 1033 - 1047. [Abstract] [Full Text] [PDF]
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S. B. Felix, A. Staudt, W. V. Dorffel, V. Stangl, K. Merkel, M. Pohl, W. D. Docke, S. Morgera, H. H. Neumayer, K. D. Wernecke, et al. Hemodynamic effects of immunoadsorption and subsequent immunoglobulin substitution in dilated cardiomyopathy: Three-month results from a randomized study J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1590 - 1598. [Abstract] [Full Text] [PDF]
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C Berry and A.L Clark Catabolism in chronic heart failure Eur. Heart J., April 1, 2000; 21(7): 521 - 532. [PDF]
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A. M. Feldman, A. Combes, D. Wagner, T. Kadakomi, T. Kubota, Y. You Li, and C. McTiernan The role of tumor necrosis factor in the pathophysiology of heart failure J. Am. Coll. Cardiol., March 1, 2000; 35(3): 537 - 544. [Abstract] [Full Text] [PDF]
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K. Sliwa, D. Skudicky, A. Bergemann, G. Candy, A. Puren, and P. Sareli Peripartum cardiomyopathy: analysis of clinical outcome, left ventricular function, plasma levels of cytokines and Fas/APO-1 J. Am. Coll. Cardiol., March 1, 2000; 35(3): 701 - 705. [Abstract] [Full Text] [PDF]
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T. Tsutamoto, A. Wada, K. Maeda, N. Mabuchi, M. Hayashi, T. Tsutsui, M. Ohnishi, M. Sawaki, M. Fujii, T. Matsumoto, et al. Angiotensin II type 1 receptor antagonist decreases plasma levels of tumor necrosis factor alpha, interleukin-6 and soluble adhesion molecules in patients with chronic heart failure J. Am. Coll. Cardiol., March 1, 2000; 35(3): 714 - 721. [Abstract] [Full Text] [PDF]
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L. Agnoletti, S. Curello, T. Bachetti, F. Malacarne, G. Gaia, L. Comini, M. Volterrani, P. Bonetti, G. Parrinello, M. Cadei, et al. Serum From Patients With Severe Heart Failure Downregulates eNOS and Is Proapoptotic : Role of Tumor Necrosis Factor-{alpha} Circulation, November 9, 1999; 100(19): 1983 - 1991. [Abstract] [Full Text] [PDF]
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L. Comini, T. Bachetti, L. Agnoletti, G. Gaia, S. Curello, B. Milanesi, M. Volterrani, G. Parrinello, C. Ceconi, A. Giordano, et al. Induction of functional inducible nitric oxide synthase in monocytes of patients with congestive heart failure. Link with tumour necrosis factor-{alpha} Eur. Heart J., October 2, 1999; 20(20): 1503 - 1513. [Abstract] [PDF]
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M. R. Bergman, R. H. Kao, S. A. McCune, and B. J. Holycross Myocardial tumor necrosis factor-alpha secretion in hypertensive and heart failure-prone rats Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H543 - H550. [Abstract] [Full Text] [PDF]
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G. S. Francis TNF-{alpha} and Heart Failure : The Difference Between Proof of Principle and Hypothesis Testing Circulation, June 29, 1999; 99(25): 3213 - 3214. [Full Text] [PDF]
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Z. Dibbs, J. Thornby, B. G. White, and D. L. Mann Natural variability of circulating levels of cytokines and cytokine receptors in patients with heart failure: implications for clinical trials J. Am. Coll. Cardiol., June 1, 1999; 33(7): 1935 - 1942. [Abstract] [Full Text] [PDF]
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G. W Moe and P. Armstrong Pacing-induced heart failure: a model to study the mechanism of disease progression and novel therapy in heart failure Cardiovasc Res, June 1, 1999; 42(3): 591 - 599. [Full Text] [PDF]
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S.D. Anker, P.P. Ponikowski, A.L. Clark, F. Leyva, M. Rauchhaus, M. Kemp, M.M. Teixeira, P.G. Hellewell, J. Hooper, P.A. Poole-Wilson, et al. Cytokines and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure Eur. Heart J., May 1, 1999; 20(9): 683 - 693. [Abstract] [PDF]
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M. W. Irwin, S. Mak, D. L. Mann, R. Qu, J. M. Penninger, A. Yan, F. Dawood, W.-H. Wen, Z. Shou, and P. Liu Tissue Expression and Immunolocalization of Tumor Necrosis Factor-{alpha} in Postinfarction Dysfunctional Myocardium Circulation, March 23, 1999; 99(11): 1492 - 1498. [Abstract] [Full Text] [PDF]
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S. D. Anker and A. J. S. Coats Cardiac Cachexia: A Syndrome With Impaired Survival and Immune and Neuroendocrine Activation Chest, March 1, 1999; 115(3): 836 - 847. [Abstract] [Full Text] [PDF]
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T. Kubota, D. M. McNamara, J. J. Wang, M. Trost, C. F. McTiernan, D. L. Mann, and A. M. Feldman Effects of Tumor Necrosis Factor Gene Polymorphisms on Patients With Congestive Heart Failure Circulation, June 30, 1998; 97(25): 2499 - 2501. [Abstract] [Full Text] [PDF]
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D. Bryant, L. Becker, J. Richardson, J. Shelton, F. Franco, R. Peshock, M. Thompson, and B. Giroir Cardiac Failure in Transgenic Mice With Myocardial Expression of Tumor Necrosis Factor-{alpha} Circulation, April 14, 1998; 97(14): 1375 - 1381. [Abstract] [Full Text] [PDF]
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B. Bozkurt, S. B. Kribbs, F. J. Clubb Jr, L. H. Michael, V. V. Didenko, P. J. Hornsby, Y. Seta, H. Oral, F. G. Spinale, and D. L. Mann Pathophysiologically Relevant Concentrations of Tumor Necrosis Factor-{alpha} Promote Progressive Left Ventricular Dysfunction and Remodeling in Rats Circulation, April 14, 1998; 97(14): 1382 - 1391. [Abstract] [Full Text] [PDF]
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T. Kubota, C. F. McTiernan, C. S. Frye, S. E. Slawson, B. H. Lemster, A. P. Koretsky, A. J. Demetris, and A. M. Feldman Dilated Cardiomyopathy in Transgenic Mice With Cardiac-Specific Overexpression of Tumor Necrosis Factor-{alpha} Circ. Res., October 19, 1997; 81(4): 627 - 635. [Abstract] [Full Text]
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T. De Marco and L. Goldman Predicting Outcomes in Severe Heart Failure Circulation, June 17, 1997; 95(12): 2597 - 2599. [Full Text]
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K. D. Aaronson, J. S. Schwartz, T.-M. Chen, K.-L. Wong, J. E. Goin, and D. M. Mancini Development and Prospective Validation of a Clinical Index to Predict Survival in Ambulatory Patients Referred for Cardiac Transplant Evaluation Circulation, June 17, 1997; 95(12): 2660 - 2667. [Abstract] [Full Text]
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R. A. Kelly and T. W. Smith Cytokines and Cardiac Contractile Function Circulation, February 18, 1997; 95(4): 778 - 781. [Full Text]
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