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. 1994 Dec;72(6):561–566. doi: 10.1136/hrt.72.6.561

Increased circulating cytokines in patients with myocarditis and cardiomyopathy.

A Matsumori 1, T Yamada 1, H Suzuki 1, Y Matoba 1, S Sasayama 1
PMCID: PMC1025643  PMID: 7857740

Abstract

OBJECTIVES--To elucidate the potential role of cytokines in the pathogenesis of cardiomyopathy and myocarditis. BACKGROUND--Experimental studies show that certain cytokines depress myocardial contractility and that tumour necrosis factor-alpha plays an important part in the pathogenesis of myocardial injury in animal models of viral and autoimmune myocarditis. METHODS--Plasma interleukin 1-alpha, interleukin 1-beta, interleukin-2, interleukin-6, tumour necrosis factor-alpha, tumour necrosis factor-beta, granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, macrophage colony stimulating factor, interferon-alpha and interferon-gamma were measured in 13 patients with acute myocarditis, 23 patients with dilated cardiomyopathy, 51 patients with hypertrophic cardiomyopathy, nine patients with acute myocardial infarction, 18 patients with angina pectoris, 12 patients with essential hypertension and 17 healthy controls. RESULTS--Increased concentrations of cytokines were not detected in the controls. In patients with acute myocarditis, interleukin 1-alpha was detected in 23% (mean (SD) 25 (11) pg/ml), tumour necrosis factor-alpha in 46% (61 (31) pg/ml), and macrophage colony stimulating factor was 2.5 (1.8) ng/ml (normal 1.9 (0.4)). In patients with dilated cardiomyopathy, tumour necrosis factor-alpha was detected in 35% (402 (555) pg/ml). In patients with hypertrophic cardiomyopathy, interleukin-2 was detectable in 14% (2318 (4738) pg/ml) and tumour necrosis factor-alpha ws detected in 20% (992 (1517) pg/ml). The concentration of macrophage colony stimulating factor was raised in patients with acute myocardial infarction. Granulocyte colony stimulating factor was often increased in myocarditis, cardiomyopathies, acute myocardial infarction, and angina pectoris--suggesting activation of macrophages and/or endothelial cells--but this increase was not specific to these diseases. Increased concentrations of cytokines were not found in patients with essential hypertension. CONCLUSION--These results suggest that cytokines may play a part in the pathogenesis of myocardial injury in myocarditis and cardiomyopathies and that further studies to explore the potential pathogenetic role of cytokines in myocardial diseases may be warranted.

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Selected References

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  1. Abelmann W. H., Lorell B. H. The challenge of cardiomyopathy. J Am Coll Cardiol. 1989 May;13(6):1219–1239. doi: 10.1016/0735-1097(89)90293-3. [DOI] [PubMed] [Google Scholar]
  2. Anderson J. L., Carlquist J. F., Hammond E. H. Deficient natural killer cell activity in patients with idiopathic dilated cardiomyopathy. Lancet. 1982 Nov 20;2(8308):1124–1127. doi: 10.1016/s0140-6736(82)92786-6. [DOI] [PubMed] [Google Scholar]
  3. Aretz H. T., Billingham M. E., Edwards W. D., Factor S. M., Fallon J. T., Fenoglio J. J., Jr, Olsen E. G., Schoen F. J. Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol. 1987 Jan;1(1):3–14. [PubMed] [Google Scholar]
  4. Arya S. K., Wong-Staal F., Gallo R. C. T-cell growth factor gene: lack of expression in human T-cell leukemia-lymphoma virus-infected cells. Science. 1984 Mar 9;223(4640):1086–1087. doi: 10.1126/science.6320374. [DOI] [PubMed] [Google Scholar]
  5. Balligand J. L., Kelly R. A., Marsden P. A., Smith T. W., Michel T. Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):347–351. doi: 10.1073/pnas.90.1.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Balligand J. L., Ungureanu D., Kelly R. A., Kobzik L., Pimental D., Michel T., Smith T. W. 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):2314–2319. doi: 10.1172/JCI116461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Caforio A. L., Grazzini M., Mann J. M., Keeling P. J., Bottazzo G. F., McKenna W. J., Schiaffino S. Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy. Circulation. 1992 May;85(5):1734–1742. doi: 10.1161/01.cir.85.5.1734. [DOI] [PubMed] [Google Scholar]
  8. Carlquist J. F., Menlove R. L., Murray M. B., O'Connell J. B., Anderson J. L. HLA class II (DR and DQ) antigen associations in idiopathic dilated cardiomyopathy. Validation study and meta-analysis of published HLA association studies. Circulation. 1991 Feb;83(2):515–522. doi: 10.1161/01.cir.83.2.515. [DOI] [PubMed] [Google Scholar]
  9. Cunnion R. E., Parrillo J. E. Myocardial dysfunction in sepsis. Recent insights. Chest. 1989 May;95(5):941–945. doi: 10.1378/chest.95.5.941. [DOI] [PubMed] [Google Scholar]
  10. Dinarello C. A., Savage N. Interleukin-1 and its receptor. Crit Rev Immunol. 1989;9(1):1–20. [PubMed] [Google Scholar]
  11. Eckstein R., Mempel W., Bolte H. D. Reduced suppressor cell activity in congestive cardiomyopathy and in myocarditis. Circulation. 1982 Jun;65(6):1224–1229. doi: 10.1161/01.cir.65.6.1224. [DOI] [PubMed] [Google Scholar]
  12. Finkel M. S., Oddis C. V., Jacob T. D., Watkins S. C., Hattler B. G., Simmons R. L. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science. 1992 Jul 17;257(5068):387–389. doi: 10.1126/science.1631560. [DOI] [PubMed] [Google Scholar]
  13. Fuhlbrigge R. C., Hogquist K. A., Unanue E. R., Chaplin D. D. Molecular biology and genetics of interleukin-1. Year Immunol. 1989;5:21–37. [PubMed] [Google Scholar]
  14. Geisterfer-Lowrance A. A., Kass S., Tanigawa G., Vosberg H. P., McKenna W., Seidman C. E., Seidman J. G. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell. 1990 Sep 7;62(5):999–1006. doi: 10.1016/0092-8674(90)90274-i. [DOI] [PubMed] [Google Scholar]
  15. Hegewisch S., Weh H. J., Hossfeld D. K. TNF-induced cardiomyopathy. Lancet. 1990 Feb 3;335(8684):294–295. doi: 10.1016/0140-6736(90)90115-l. [DOI] [PubMed] [Google Scholar]
  16. Henke A., Mohr C., Sprenger H., Graebner C., Stelzner A., Nain M., Gemsa D. Coxsackievirus B3-induced production of tumor necrosis factor-alpha, IL-1 beta, and IL-6 in human monocytes. J Immunol. 1992 Apr 1;148(7):2270–2277. [PubMed] [Google Scholar]
  17. Hocking D. C., Phillips P. G., Ferro T. J., Johnson A. Mechanisms of pulmonary edema induced by tumor necrosis factor-alpha. Circ Res. 1990 Jul;67(1):68–77. doi: 10.1161/01.res.67.1.68. [DOI] [PubMed] [Google Scholar]
  18. Kawai C., Matsumori A., Fujiwara H. Myocarditis and dilated cardiomyopathy. Annu Rev Med. 1987;38:221–239. doi: 10.1146/annurev.me.38.020187.001253. [DOI] [PubMed] [Google Scholar]
  19. Kawakami M., Tsutsumi H., Kumakawa T., Abe H., Hirai M., Kurosawa S., Mori M., Fukushima M. Levels of serum granulocyte colony-stimulating factor in patients with infections. Blood. 1990 Nov 15;76(10):1962–1964. [PubMed] [Google Scholar]
  20. Koeffler H. P., Gasson J., Ranyard J., Souza L., Shepard M., Munker R. Recombinant human TNF alpha stimulates production of granulocyte colony-stimulating factor. Blood. 1987 Jul;70(1):55–59. [PubMed] [Google Scholar]
  21. Kroemer G., Gastinel L. N., Neu N., Auffray C., Wick G. How many genes code for organ-specific autoimmunity? Autoimmunity. 1990;6(3):215–233. doi: 10.3109/08916939009041042. [DOI] [PubMed] [Google Scholar]
  22. Kroemer G., Neu N., Kuehr T., Dietrich H., Fässler R., Hala K., Wick G. Immunogenetic analysis of spontaneous autoimmune thyroiditis of obese strain chickens. Clin Immunol Immunopathol. 1989 Aug;52(2):202–213. doi: 10.1016/0090-1229(89)90172-4. [DOI] [PubMed] [Google Scholar]
  23. Lane J. R., Neumann D. A., Lafond-Walker A., Herskowitz A., Rose N. R. Interleukin 1 or tumor necrosis factor can promote Coxsackie B3-induced myocarditis in resistant B10.A mice. J Exp Med. 1992 Apr 1;175(4):1123–1129. doi: 10.1084/jem.175.4.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Levine B., Kalman J., Mayer L., Fillit H. M., Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990 Jul 26;323(4):236–241. doi: 10.1056/NEJM199007263230405. [DOI] [PubMed] [Google Scholar]
  25. Maisch B. Retrospective and perspectives in the immunology of cardiac diseases. Springer Semin Immunopathol. 1989;11(4):479–482. doi: 10.1007/BF00201884. [DOI] [PubMed] [Google Scholar]
  26. Matsumori A., Hirose K., Wakabayashi A., Kawai C., Nabeya N., Sakurami T., Tsuji K. HL-A and hypertrophic cardiomyopathy. Am Heart J. 1979 Apr;97(4):428–431. doi: 10.1016/0002-8703(79)90387-9. [DOI] [PubMed] [Google Scholar]
  27. Matsumori A., Kawai C., Wakabayashi A., Terasaki P. I., Park M. S., Sakurami T., Ueno Y. HLA-DRW4 antigen linkage in patients with hypertrophic obstructive cardiomyopathy. Am Heart J. 1981 Jan;101(1):14–16. doi: 10.1016/0002-8703(81)90377-x. [DOI] [PubMed] [Google Scholar]
  28. Maury C. P., Teppo A. M. Circulating tumour necrosis factor-alpha (cachectin) in myocardial infarction. J Intern Med. 1989 May;225(5):333–336. doi: 10.1111/j.1365-2796.1989.tb00090.x. [DOI] [PubMed] [Google Scholar]
  29. McMurray J., Abdullah I., Dargie H. J., Shapiro D. Increased concentrations of tumour necrosis factor in "cachectic" patients with severe chronic heart failure. Br Heart J. 1991 Nov;66(5):356–358. doi: 10.1136/hrt.66.5.356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schultheiss H. P. The significance of autoantibodies against the ADP/ATP carrier for the pathogenesis of myocarditis and dilated cardiomyopathy--clinical and experimental data. Springer Semin Immunopathol. 1989;11(1):15–30. doi: 10.1007/BF00197081. [DOI] [PubMed] [Google Scholar]
  31. Smith S. C., Allen P. M. Neutralization of endogenous tumor necrosis factor ameliorates the severity of myosin-induced myocarditis. Circ Res. 1992 Apr;70(4):856–863. doi: 10.1161/01.res.70.4.856. [DOI] [PubMed] [Google Scholar]
  32. Tominaga M., Matsumori A., Horie M., Yoshida H., Okada Y. Activation of Ca-permeable cation channels by myocarditis-associated antibody in guinea pig ventricular myocytes. J Clin Invest. 1993 Mar;91(3):1231–1234. doi: 10.1172/JCI116285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tracey K. J., Lowry S. F., Beutler B., Cerami A., Albert J. D., Shires G. T. Cachectin/tumor necrosis factor mediates changes of skeletal muscle plasma membrane potential. J Exp Med. 1986 Oct 1;164(4):1368–1373. doi: 10.1084/jem.164.4.1368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Watkins H., Rosenzweig A., Hwang D. S., Levi T., McKenna W., Seidman C. E., Seidman J. G. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med. 1992 Apr 23;326(17):1108–1114. doi: 10.1056/NEJM199204233261703. [DOI] [PubMed] [Google Scholar]
  35. Yamada T., Matsumori A., Sasayama S. Therapeutic effect of anti-tumor necrosis factor-alpha antibody on the murine model of viral myocarditis induced by encephalomyocarditis virus. Circulation. 1994 Feb;89(2):846–851. doi: 10.1161/01.cir.89.2.846. [DOI] [PubMed] [Google Scholar]

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