Logo of brheartjLink to Publisher's site
Br Heart J. Dec 1994; 72(6): 561–566.
PMCID: PMC1025643

Increased circulating cytokines in patients with myocarditis and cardiomyopathy.


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Maury CP, Teppo AM. Circulating tumour necrosis factor-alpha (cachectin) in myocardial infarction. J Intern Med. 1989 May;225(5):333–336. [PubMed]
  • 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 Jul 26;323(4):236–241. [PubMed]
  • McMurray J, Abdullah I, Dargie HJ, 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. [PMC free article] [PubMed]
  • Hocking DC, Phillips PG, Ferro TJ, Johnson A. Mechanisms of pulmonary edema induced by tumor necrosis factor-alpha. Circ Res. 1990 Jul;67(1):68–77. [PubMed]
  • Tracey KJ, Lowry SF, Beutler B, Cerami A, Albert JD, Shires GT. Cachectin/tumor necrosis factor mediates changes of skeletal muscle plasma membrane potential. J Exp Med. 1986 Oct 1;164(4):1368–1373. [PMC free article] [PubMed]
  • Cunnion RE, Parrillo JE. Myocardial dysfunction in sepsis. Recent insights. Chest. 1989 May;95(5):941–945. [PubMed]
  • Lane JR, Neumann DA, Lafond-Walker A, Herskowitz A, Rose NR. 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JJ, Jr, Olsen EG, Schoen FJ. Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol. 1987 Jan;1(1):3–14. [PubMed]
  • Fuhlbrigge RC, Hogquist KA, Unanue ER, Chaplin DD. Molecular biology and genetics of interleukin-1. Year Immunol. 1989;5:21–37. [PubMed]
  • Dinarello CA, Savage N. Interleukin-1 and its receptor. Crit Rev Immunol. 1989;9(1):1–20. [PubMed]
  • Kroemer G, Gastinel LN, Neu N, Auffray C, Wick G. How many genes code for organ-specific autoimmunity? Autoimmunity. 1990;6(3):215–233. [PubMed]
  • 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. [PubMed]
  • Hegewisch S, Weh HJ, Hossfeld DK. TNF-induced cardiomyopathy. Lancet. 1990 Feb 3;335(8684):294–295. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Smith SC, Allen PM. Neutralization of endogenous tumor necrosis factor ameliorates the severity of myosin-induced myocarditis. Circ Res. 1992 Apr;70(4):856–863. [PubMed]
  • 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]
  • Kawai C, Matsumori A, Fujiwara H. Myocarditis and dilated cardiomyopathy. Annu Rev Med. 1987;38:221–239. [PubMed]
  • Abelmann WH, Lorell BH. The challenge of cardiomyopathy. J Am Coll Cardiol. 1989 May;13(6):1219–1239. [PubMed]
  • Schultheiss HP. 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. [PubMed]
  • Maisch B. Retrospective and perspectives in the immunology of cardiac diseases. Springer Semin Immunopathol. 1989;11(4):479–482. [PubMed]
  • Caforio AL, Grazzini M, Mann JM, Keeling PJ, Bottazzo GF, McKenna WJ, 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. [PubMed]
  • Eckstein R, Mempel W, Bolte HD. Reduced suppressor cell activity in congestive cardiomyopathy and in myocarditis. Circulation. 1982 Jun;65(6):1224–1229. [PubMed]
  • Anderson JL, Carlquist JF, Hammond EH. Deficient natural killer cell activity in patients with idiopathic dilated cardiomyopathy. Lancet. 1982 Nov 20;2(8308):1124–1127. [PubMed]
  • Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattler BG, Simmons RL. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science. 1992 Jul 17;257(5068):387–389. [PubMed]
  • Balligand JL, Kelly RA, Marsden PA, Smith TW, 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. [PMC free article] [PubMed]
  • Balligand JL, Ungureanu D, Kelly RA, Kobzik L, Pimental D, Michel T, Smith TW. 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Matsumori A, Kawai C, Wakabayashi A, Terasaki PI, Park MS, Sakurami T, Ueno Y. HLA-DRW4 antigen linkage in patients with hypertrophic obstructive cardiomyopathy. Am Heart J. 1981 Jan;101(1):14–16. [PubMed]
  • Carlquist JF, Menlove RL, Murray MB, O'Connell JB, Anderson JL. 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. [PubMed]
  • Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell. 1990 Sep 7;62(5):999–1006. [PubMed]
  • Watkins H, Rosenzweig A, Hwang DS, Levi T, McKenna W, Seidman CE, Seidman JG. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med. 1992 Apr 23;326(17):1108–1114. [PubMed]
  • 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]
  • Koeffler HP, 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]
  • Arya SK, Wong-Staal F, Gallo RC. 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. [PubMed]

Articles from British Heart Journal are provided here courtesy of BMJ Group


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...