Soluble tumor necrosis factor receptors are elevated in relation to severity of congestive heart failure.

The level of tumor necrosis factor alpha (TNF-alpha) is increased in patients with congestive heart failure and may play an important role in the development and progression of heart failure. Two types of TNF receptor (TNF-RI and TNF-RII) are expressed in virtually every cell and have different biologic roles. Soluble forms of the two receptors (sTNF-RI and sTNF-RII) have been identified as extracellular domain fragments. Serum levels of TNF-alpha, sTNF-RI and sTNF-RII were measured in 66 patients with heart failure and 27 control subjects using an enzyme-linked immunosorbent assay (ELISA). Hemodynamic variables, norepinephrine, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) were evaluated. TNF-alpha was significantly higher in patients with heart failure than in controls subjects (9.4 +/- 1.4 vs 4.8 +/- 0.8 pg/ml; p < 0.05). sTNF-RI and -RII were significantly increased in relation to the severity of heart failure (control subjects, 0.66 +/- 0.04 and 1.97 +/- 0.15 ng/ml; NYHA class II, 1.10 +/- 0.08 and 2.28 +/- 0.12 ng/ml; NYHA class III, 1.63 +/- 0.22 and 3.00 +/- 0.24 ng/ml; NYHA class IV, 2.78 +/- 0.46 and 4.52 +/- 0.62 ng/ml, respectively). In 9 patients whose clinical symptoms improved after treatment, the levels of sTNF-RI and -RII decreased by 17.3 +/- 5.7% (p < 0.05) and 22.1 +/- 6.9% (p < 0.05), respectively. There were significant positive correlations between sTNF-RI and -RII and mean pulmonary pressure (r = 0.69 and r = 0.61; p < 0.001) and mean capillary wedge pressure (r = 0.65 and r = 0.54; p < 0.001 and p < 0.01, respectively), but not with left ventricular end-diastolic volume or ejection fraction (NS). sTNF-RI and -RII were also significantly positively correlated with plasma levels of norepinephrine (r = 0.75 and r = 0.50; p < 0.001 and p < 0.05), ANP (r = 0.72 and r = 0.70; p < 0.001), and BNP (r = 0.60 and r = 0.60; p < 0.001). In conclusion, soluble TNF receptors are increased in proportion to the severity of congestive heart failure and may reflect the current status of congestive heart failure rather than the level of left ventricular dysfunction.

[1]  H. Oral,et al.  Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). , 1996, Journal of the American College of Cardiology.

[2]  D. Mann,et al.  Tumor Necrosis Factor-α and Tumor Necrosis Factor Receptors in the Failing Human Heart , 1996 .

[3]  D. Fukai,et al.  Prognostic value of plasma soluble intercellular adhesion molecule-1 and endothelin-1 concentration in patients with chronic congestive heart failure. , 1995, The American journal of cardiology.

[4]  W. Fiers,et al.  Two tumour necrosis factor receptors: structure and function. , 1995, Trends in cell biology.

[5]  O. Febo,et al.  Tumor necrosis factor soluble receptors in patients with various degrees of congestive heart failure. , 1995, Circulation.

[6]  T. LeJemtel,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 , 1994, Circulation.

[7]  W. Buurman,et al.  Lipopolysaccharide LPS-mediated soluble TNF receptor release and TNF receptor expression by monocytes. Role of CD14, LPS binding protein, and bactericidal/permeability-increasing protein. , 1994, Journal of immunology.

[8]  S Sasayama,et al.  Vesnarinone, a new inotropic agent, inhibits cytokine production by stimulated human blood from patients with heart failure. , 1994, Circulation.

[9]  L. Vaca,et al.  Cellular basis for the negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian heart. , 1993, The Journal of clinical investigation.

[10]  C. Suschek,et al.  Induction of a macrophage-like nitric oxide synthase in cultured rat aortic endothelial cells. IL-1 beta-mediated induction regulated by tumor necrosis factor-alpha and IFN-gamma. , 1993, Journal of immunology.

[11]  A. Cope,et al.  Correlation between serum levels of soluble tumor necrosis factor receptor and disease activity in systemic lupus erythematosus. , 1993, Arthritis and rheumatism.

[12]  G. Morris,et al.  Tumour necrosis factor alpha in severe congestive cardiac failure. , 1993, British heart journal.

[13]  B. Aggarwal,et al.  Okadaic acid induces down-modulation and shedding of tumor necrosis factor receptors. Comparison with another tumor promoter, phorbol ester. , 1993, The Journal of biological chemistry.

[14]  M. Brockhaus,et al.  Release of soluble receptors for tumor necrosis factor (TNF) in relation to circulating TNF during experimental endotoxinemia. , 1992, The Journal of clinical investigation.

[15]  F. Pagani,et al.  Left ventricular systolic and diastolic dysfunction after infusion of tumor necrosis factor-alpha in conscious dogs. , 1992, The Journal of clinical investigation.

[16]  Simon C Watkins,et al.  Negative inotropic effects of cytokines on the heart mediated by nitric oxide. , 1992, Science.

[17]  L. Moldawer,et al.  Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alpha in vitro and in vivo. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[18]  P. Suter,et al.  Imbalance between tumour necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia. The J5 Study Group. , 1992, Immunology.

[19]  D. Kioussis,et al.  Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. , 1991, The EMBO journal.

[20]  T. Gatanaga,et al.  The regulation of TNF receptor mRNA synthesis, membrane expression, and release by PMA- and LPS-stimulated human monocytic THP-1 cells in vitro. , 1991, Cellular immunology.

[21]  J. McMurray,et al.  Increased concentrations of tumour necrosis factor in "cachectic" patients with severe chronic heart failure. , 1991, British heart journal.

[22]  D. Wallach,et al.  Increased serum levels of soluble receptors for tumor necrosis factor in cancer patients. , 1991, Cancer research.

[23]  J. Vilček,et al.  Tumor necrosis factor. New insights into the molecular mechanisms of its multiple actions. , 1991, The Journal of biological chemistry.

[24]  K. Inouye,et al.  Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide. , 1991, The Journal of clinical investigation.

[25]  U. Gullberg,et al.  Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor. , 1990, The Journal of clinical investigation.

[26]  R. Heller,et al.  Complementary DNA cloning of a receptor for tumor necrosis factor and demonstration of a shed form of the receptor. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[27]  H. Fillit,et al.  Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. , 1990, The New England journal of medicine.

[28]  R. Gentz,et al.  Two human TNF receptors have similar extracellular, but distinct intracellular, domain sequences. , 1990, Cytokine.

[29]  J. Adams,et al.  hypotension: Implications for the involvement of nitric oxide , 2022 .

[30]  G. Wong,et al.  Molecular cloning and expression of a receptor for human tumor necrosis factor , 1990, Cell.

[31]  D. Hossfeld,et al.  TNF-induced cardiomyopathy , 1990, The Lancet.

[32]  D. Wallach,et al.  Two tumor necrosis factor-binding proteins purified from human urine. Evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors. , 1990, The Journal of biological chemistry.

[33]  D. Wallach,et al.  A tumor necrosis factor-binding protein purified to homogeneity from human urine protects cells from tumor necrosis factor toxicity. , 1989, The Journal of biological chemistry.

[34]  Kevin J. Tracey,et al.  Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia , 1987, Nature.

[35]  Andrew,et al.  Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion. , 1986, The Journal of clinical investigation.

[36]  J. Cohn,et al.  Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. , 1984, The New England journal of medicine.

[37]  R L Kassel,et al.  An endotoxin-induced serum factor that causes necrosis of tumors. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[38]  H. Loetscher,et al.  Tumor necrosis factor receptors-structure and function , 1992, Immunologic research.