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PMID: 8642298 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum.

The Journal of experimental medicine ·Vol. 183 ·No. 3 ·1996-03-01 ·Pages 949-58

Kumar A, Thota V, Dee L, Olson J, Uretz E, Parrillo JE

Abstract

Previous studies have demonstrated the presence of myocardial depression in clinical and experimental septic shock. This depression is associated with the presence of a circulating myocardial depressant substance with physical characteristics consistent with cytokines. The present study utilized an in vitro myocardial cell assay to examine the role of various human recombinant cytokines, including tumor necrosis factor (TNF)alpha and interleukin (IL)1beta, in depression of cardiac myocyte contractile function induced by serum from humans with septic shock. The extent and velocity of electrically paced rat cardiac myocytes in tissue culture was quantified by a closed loop video tracking system. Individually, TNF-alpha and IL-1beta each caused significant concentration-dependent depression of maximum extent and peak velocity of myocyte shortening in vitro. In combination, TNF-alpha and IL-1beta induced depression of myocardial cell contractility at substantially lower concentrations consistent with a synergistic effect. Using immunoabsorption, removal of both TNF-alpha and IL-1beta (but not either alone) from the serum of five patients with acute septic shock and marked reversible myocardial depression resulted in elimination of serum myocardial depressant activity. IL-2, -4, -6, -8, -10, and interferon gamma failed to cause significant cardiac myocyte depression over a wide range of concentrations. These data demonstrate that TNF-alpha and IL-1beta cause depression of myocardial cell contraction in vitro and suggest that these two cytokines act synergistically to cause sepsis-associated myocardial depression in humans.

MeSH Terms
Animals Cytokines/pharmacology Dose-Response Relationship, Drug Heart/drug effects,physiology Humans In Vitro Techniques Interferon-gamma/pharmacology Interleukin-1/pharmacology Interleukins/pharmacology Kinetics Male Myocardial Contraction/drug effects,immunology Myocardium/immunology Rats Rats, Inbred Lew Recombinant Proteins/pharmacology Shock, Septic/blood,immunology Time Factors Tumor Necrosis Factor-alpha/pharmacology
Chemicals
Cytokines Interleukin-1 Interleukins Recombinant Proteins Tumor Necrosis Factor-alpha Interferon-gamma
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kumar A
Department of Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Thota V
Dee L
Olson J
Uretz E
Parrillo J E
References (41)
41 references, click to expand
  1. Interleukin 1 potentiates the lethal effect of tumor necrosis factor alpha/cachectin in mice.
    J Exp Med. 1988 Jun 1;167(6):1987-92 PMID: 3290384
  2. Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition.
    J Clin Invest. 1988 Apr;81(4):1162-72 PMID: 3258319
  3. The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome.
    J Exp Med. 1989 Jan 1;169(1):333-8 PMID: 2783334
  4. Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock.
    J Exp Med. 1989 Mar 1;169(3):823-32 PMID: 2647895
  5. A circulating myocardial depressant substance is associated with cardiac dysfunction and peripheral hypoperfusion (lactic acidemia) in patients with septic shock.
    Chest. 1989 May;95(5):1072-80 PMID: 2707065
  6. Interleukin 1 and tumor necrosis factor inhibit cardiac myocyte beta-adrenergic responsiveness.
    Proc Natl Acad Sci U S A. 1989 Sep;86(17):6753-7 PMID: 2549546
  7. Right ventricular dysfunction and dilatation, similar to left ventricular changes, characterize the cardiac depression of septic shock in humans.
    Chest. 1990 Jan;97(1):126-31 PMID: 2295231
  8. Immediate release of a nitric oxide-like factor from bovine aortic endothelial cells by Escherichia coli lipopolysaccharide.
    Proc Natl Acad Sci U S A. 1990 Apr;87(7):2593-7 PMID: 2181441
  9. Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy.
    Ann Intern Med. 1990 Aug 1;113(3):227-42 PMID: 2197912
  10. Mechanism of cytokine inhibition of beta-adrenergic agonist stimulation of cyclic AMP in rat cardiac myocytes. Impairment of signal transduction.
    Circ Res. 1990 Sep;67(3):753-63 PMID: 2168817
  11. Endotoxemia in human septic shock.
    Chest. 1991 Jan;99(1):169-75 PMID: 1984950
  12. Induction and potential biological relevance of a Ca(2+)-independent nitric oxide synthase in the myocardium.
    Br J Pharmacol. 1992 Mar;105(3):575-80 PMID: 1378338
  13. Negative inotropic effects of cytokines on the heart mediated by nitric oxide.
    Science. 1992 Jul 17;257(5068):387-9 PMID: 1631560
  14. Lipopolysaccharide, tumor necrosis factor, and interleukin-1 interact to cause hypotension.
    J Lab Clin Med. 1992 Aug;120(2):205-11 PMID: 1500820
  15. Tumor necrosis factor challenges in canines: patterns of cardiovascular dysfunction.
    Am J Physiol. 1992 Sep;263(3 Pt 2):H668-75 PMID: 1415590
  16. Role of nitric oxide in antagonistic effects of transforming growth factor-beta and interleukin-1 beta on the beating rate of cultured cardiac myocytes.
    Mol Endocrinol. 1992 Nov;6(11):1921-30 PMID: 1282674
  17. Pathogenetic mechanisms of septic shock.
    N Engl J Med. 1993 May 20;328(20):1471-7 PMID: 8479467
  18. Abnormal contractile function due to induction of nitric oxide synthesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium.
    J Clin Invest. 1993 May;91(5):2314-9 PMID: 8486792
  19. Effects of E. coli sepsis and myocardial depressant factor on interval-force relations in dog ventricle.
    Am J Physiol. 1993 May;264(5 Pt 2):H1402-10 PMID: 8498554
  20. The effects of interleukin 1 on myocardial function and metabolism.
    Clin Immunol Immunopathol. 1993 Aug;68(2):175-80 PMID: 7689429
  21. Effects of cytokines on the contractility of cultured cardiac myocytes.
    Int J Immunopharmacol. 1993 Jul;15(5):581-7 PMID: 8375940
  22. Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome.
    Ann Intern Med. 1993 Oct 15;119(8):771-8 PMID: 8379598
  23. Interleukin-1 beta modulates myocardial contraction via dexamethasone sensitive production of nitric oxide.
    Cardiovasc Res. 1993 Aug;27(8):1486-90 PMID: 8221802
  24. Cellular basis for the negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian heart.
    J Clin Invest. 1993 Nov;92(5):2303-12 PMID: 8227345
  25. Decrease in left ventricular contractility after tumor necrosis factor-alpha infusion in dogs.
    J Appl Physiol (1985). 1994 Mar;76(3):1060-7 PMID: 8005845
  26. Nitric oxide-mediated effects of interleukin-6 on [Ca2+]i and cell contraction in cultured chick ventricular myocytes.
    Circ Res. 1994 Aug;75(2):285-95 PMID: 7518362
  27. In vitro studies of single isolated beating heart cells.
    Science. 1960 Jun 3;131(3414):1674-5 PMID: 14399673
  28. Origin of myocardial depressant factor in shock.
    Am J Physiol. 1970 May;218(5):1423-7 PMID: 5438272
  29. Relationship between splanchnic blood flow and a myocardial depressant factor in endotoxin shock.
    Surgery. 1971 Mar;69(3):410-8 PMID: 5544894
  30. Presence of a myocardial depressant factor in patients in circulatory shock.
    Surgery. 1971 Aug;70(2):223-31 PMID: 5560183
  31. Reversal by calcium of rat heart cell dysfunction induced by human sera in septic shock.
    Circ Shock. 1979;6(2):147 PMID: 455596
  32. Is there a humoral factor that depresses ventricular function in sepsis?
    Circ Shock Suppl. 1979;1:9-22 PMID: 288535
  33. Profound but reversible myocardial depression in patients with septic shock.
    Ann Intern Med. 1984 Apr;100(4):483-90 PMID: 6703540
  34. Early released lipid-soluble cardiodepressant factor and elevated oestrogenic substances in human septic shock.
    Eur J Clin Invest. 1984 Aug;14(4):288-94 PMID: 6434324
  35. Left ventricular performance in septic shock: reversible segmental and global abnormalities.
    Am Heart J. 1985 Aug;110(2):402-9 PMID: 4025116
  36. A circulating myocardial depressant substance in humans with septic shock. Septic shock patients with a reduced ejection fraction have a circulating factor that depresses in vitro myocardial cell performance.
    J Clin Invest. 1985 Oct;76(4):1539-53 PMID: 4056039
  37. Gram-negative bacteremia produces both severe systolic and diastolic cardiac dysfunction in a canine model that simulates human septic shock.
    J Clin Invest. 1986 Jul;78(1):259-70 PMID: 3722379
  38. Left ventricular function during lethal and sublethal endotoxemia in swine.
    Am J Physiol. 1986 Aug;251(2 Pt 2):H364-73 PMID: 3526928
  39. Closed loop television tracking of beating heart cells in vitro.
    Cytometry. 1987 Jan;8(1):101-3 PMID: 3803092
  40. Cardiovascular performance with E. coli challenges in a canine model of human sepsis.
    Am J Physiol. 1988 Mar;254(3 Pt 2):H558-69 PMID: 3279822
  41. Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura.
    N Engl J Med. 1988 Aug 18;319(7):397-400 PMID: 3135497
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.183.3.949
Published
1996-03-01
Pages
949-58
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192364
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.183.3.949 PMC Full Text View journal details
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