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Serum concentrations of interleukin-4 and interferon-gamma in relation to severe left ventricular dysfunction in patients with acute myocardial infarction undergoing percutaneous coronary intervention

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Abstract

Many studies have suggested an imbalance between proinflammatory and anti-inflammatory markers in acute myocardial infarction (AMI). Interleukin 4 (IL-4) shows mainly anti-inflammatory activities. Interferon-gamma (IFN-γ) is a proinflammatory cytokine secreted by Th1 lymphocytes. Severe systolic left ventricular (LV) dysfunction following AMI is one of the major risk factors for poor prognosis. The aim of this study was to evaluate whether IL-4 and IFN-γ concentrations can serve as the correlates of impaired left ventricular function. Fifty-three patients with AMI were enrolled and divided into two groups depending on their ejection fraction (EF): group 1 with EF ≤30% (N = 10) and group 2 with EF >30% (N = 43). All patients underwent coronary angiography followed by percutaneous coronary intervention (PCI). Blood samples were taken (1) before, (2) immediately after, (3) 2 h after, and (4) 72 h after PCI. A receiver-operating characteristic (ROC) analysis was planned to identify possible cutoff values to predict LV dysfunction. There was no sex difference between the two groups. The rate of hypertension and diabetes mellitus was also similar. Median concentrations for IL-4 (pg/ml) were: (1) 13.4 versus 17.2 (p = 0.0001), (2) 16.8 versus 18.6 (p = 0.01), (3) 17.2 versus 17.6 (p = NS), and (4) 17.6 versus 17.2 (p = NS). Median concentrations for IFNγ (pg/ml) were: (1) 0.3 versus 1.9 (p = 0.00001), (2) 2.1 versus 1.6 (p = NS), (3) 0.4 versus 0.9 (p = NS), and (4) 0.9 versus 1.1 (p = NS). The area under the ROC curve (AUC) analysis is presented in the table below. Reported results suggest the high diagnostic value of IL-4 measurements before and immediately after PCI as the correlates of impaired LV dysfunction, whereas only IFN-γ measurement before PCI had a high diagnostic value. Measurements performed later on have no predictive value.

 

Cutoff value

AUC

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

p

IL-4 (a)

≤15.0

0.89

100

79

52

100

0.0001

IL-4 (b)

≤17.2

0.75

100

67

42

100

0.0007

IFNγ (a)

≤0.3

0.94

100

91

71

100

0.0001

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References

  1. Cohn JN, Ferrari R, Sharpe N (2000) Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol 35:569–582

    Article  PubMed  CAS  Google Scholar 

  2. Mann DL, Young JB (1994) Basic mechanisms in congestive heart failure. Recognizing the role of proinflammatory cytokines. Chest 105:897–904

    Article  PubMed  CAS  Google Scholar 

  3. De Gennaro L, Brunetti ND, Cuculo A, Pellegrino PL, Di Biase M (2008) Systemic inflammation in nonischemic dilated cardiomyopathy. Heart Vessels 23:445–450

    Article  PubMed  Google Scholar 

  4. Chrysohoou C, Pitsavos C, Barbetseas J, Kotroyiannis I, Brili S, Vasiliadou K, Papadimitriou L, Stefanadis C (2009) Chronic systemic inflammation accompanies impaired ventricular diastolic function, detected by Doppler imaging, in patients with newly diagnosed systolic heart failure (Hellenic Heart Failure Study). Heart Vessels 24:22–26

    Article  PubMed  Google Scholar 

  5. Yamaoka M, Yamaguchi S, Okuyama M, Tomoike H (1999) Anti-inflammatory cytokine profile in human heart failure: behavior of interleukin-10 in association with tumor necrosis factor-alpha. Jpn Circ J 63:951–956

    Article  PubMed  CAS  Google Scholar 

  6. Torre-Amione G, Kapadia S, Lee J, Durand JB, Bies RD, Young JB, Mann DL (1996) Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart. Circulation 93:704–711

    PubMed  CAS  Google Scholar 

  7. Tsutamoto T, Hisanaga T, Wada A, Maeda K, Ohnishi M, Fukai D, Mabuchi N, Sawaki M, Kinoshita M (1998) Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J Am Coll Cardiol 31:391–398

    Article  PubMed  CAS  Google Scholar 

  8. Kaur K, Sharma AK, Singal PK (2006) Significance of changes in TNF-alpha and IL-10 levels in the progression of heart failure subsequent to myocardial infarction. Am J Physiol Heart Circ Physiol 291:H106–H113

    Article  PubMed  CAS  Google Scholar 

  9. Kaur K, Dhingra S, Slezak J, Sharma AK, Bajaj A, Singal PK (2009) Biology of TNF alpha and IL-10, and their imbalance in heart failure. Heart Fail Rev 14:113–123

    Article  PubMed  CAS  Google Scholar 

  10. Fukunaga T, Soejima H, Irie A, Sugamura K, Oe Y, Tanaka T, Kojima S, Sakamoto T, Yoshimura M, Nishimura Y, Ogawa H (2007) Expression of interferon-gamma and interleukin-4 production in CD4+ T cells in patients with chronic heart failure. Heart Vessels 22:178–183

    Article  PubMed  Google Scholar 

  11. Jug B, Salobir BG, Vene N, Sebestjen M, Sabovic M, Keber I (2009) Interleukin-6 is a stronger prognostic predictor than high-sensitive C-reactive protein in patients with chronic stable heart failure. Heart Vessels 24:271–276

    Article  PubMed  Google Scholar 

  12. Yao HC, Liu SQ, Yu K, Zhou M, Wang LX (2009) Interleukin-2 enhances the cytotoxic activity of circulating natural killer cells in patients with chronic heart failure. Heart Vessels 24:283–286

    Article  PubMed  Google Scholar 

  13. Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, Filippatos G, Fox K, Huber K, Kastrati A, Rosengren A, Steg PG, Tubaro M, Verheugt F, Weidinger F, Weis M, ESC Committee for Practice Guidelines (CPG), Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Silber S, Aguirre FV, Al-Attar N, Alegria E, Andreotti F, Benzer W, Breithardt O, Danchin N, Di Mario C, Dudek D, Gulba D, Halvorsen S, Kaufmann P, Kornowski R, Lip GY, Rutten F (2008) Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the task force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology. Eur Heart J 29:2909–2945

    Article  PubMed  Google Scholar 

  14. Hudzik B, Szkodzinski J, Danikiewicz A, Romanowski W, Lekston A, Polonski L, Zubelewicz-Szkodzinska B (2010) Serum interleukin-6 concentration predicts contrast-induced nephropathy in patients undergoing percutaneous coronary intervention. Eur Cytokine Netw 21:129–135

    PubMed  CAS  Google Scholar 

  15. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ, Chamber Quantification Writing Group; American Society of Echocardiography’s Guidelines Standards Committee; European Association of Echocardiography (2005) Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 18:1440–1463

    Article  PubMed  Google Scholar 

  16. Mann DL (1999) Mechanisms and models in heart failure: a combinatorial approach. Circulation 100:999–1008

    PubMed  CAS  Google Scholar 

  17. te Velde AA, Huijbens RJ, Heije K, de Vries JE, Figdor CG (1990) Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes. Blood 76:1392–1397

    PubMed  CAS  Google Scholar 

  18. Bijlsma FJ, van Kuik J, van Hoffen E, de Jonge N, Tilanus MG, Gmelig-Meyling FH, de Weger RA (2002) Acute cardiac transplant rejection is associated with low frequencies of interleukin-4 producing helper T-lymphocytes rather than with interleukin-4 promoter or splice variants. Hum Immunol 63:317–323

    Article  PubMed  CAS  Google Scholar 

  19. Paffen E, Medina P, de Visser MC, van Wijngaarden A, Zorio E, Estellés A, Rosendaal FR, Espana F, Bertina RM, Doggen CJ (2008) The −589C> T polymorphism in the interleukin-4 gene (IL-4) is associated with a reduced risk of myocardial infarction in young individuals. J Thromb Haemost 6:1633–1638

    Article  PubMed  CAS  Google Scholar 

  20. Mostafa Mtairag E, Chollet-Martin S, Oudghiri M, Laquay N, Jacob MP, Michel JB, Feldman LJ (2001) Effects of interleukin-10 on monocyte/endothelial cell adhesion and MMP-9/TIMP-1 secretion. Cardiovasc Res 49:882–890

    Article  PubMed  CAS  Google Scholar 

  21. Opal SM, DePalo VA (2000) Anti-inflammatory cytokines. Chest 117:1162–1172

    Article  PubMed  CAS  Google Scholar 

  22. Karpinski L, Plaksej R, Kosmala W, Witkowska M (2008) Serum levels of interleukin-6, interleukin-10 and C-reactive protein in relation to left ventricular function in patients with myocardial infarction treated with primary angioplasty. Kardiol Pol 66:1279–1285

    PubMed  Google Scholar 

  23. Yndestad A, Holm AM, Muller F, Simonsen S, Froland SS, Gullestad L, Aukrust P (2003) Enhanced expression of inflammatory cytokines and activation markers in T-cells from patients with chronic heart failure. Cardiovasc Res 60:141–146

    Article  PubMed  CAS  Google Scholar 

  24. Morino Y, Hara K, Ushikoshi H, Tanabe K, Kuroda Y, Noguchi T, Ayabe S, Hara H, Yanbe Y, Kozuma K, Ikari Y, Saeki F, Tamura T (2000) γ-Interferon-induced cardiomyopathy during treatment of renal cell carcinoma: a case report. J Cardiol 36:49–57

    PubMed  CAS  Google Scholar 

  25. Reifenberg K, Lehr HA, Torzewski M, Steige G, Wiese E, Küpper I, Becker C, Ott S, Nusser P, Yamamura K, Rechtsteiner G, Warger T, Pautz A, Kleinert H, Schmidt A, Pieske B, Wenzel P, Münzel T, Löhler J (2007) Interferon-gamma induces chronic active myocarditis and cardiomyopathy in transgenic mice. Am J Pathol 171:463–472

    Article  PubMed  CAS  Google Scholar 

  26. Sartori M, Andorno S, La Terra G, Pozzoli G, Rudoni M, Sacchetti GM, Inglese E, Aglietta M (1995) Assessment of interferon cardiotoxicity with quantitative radionuclide angiocardiography. Eur J Clin Invest 25:68–70

    Article  PubMed  CAS  Google Scholar 

  27. Sardella G, De Luca L, Francavilla V, Accapezzato D, Di Roma A, Gianoglio O, Colantonio R, Mancone M, Fedele F, Paroli M (2007) Effect of coronary percutaneous revascularization on interferon-gamma and interleukin-10 producing CD4+ T cells during acute myocardial infarction. Int J Immunopathol Pharmacol 20:791–799

    PubMed  CAS  Google Scholar 

  28. Hands ME, Antico V, Thompson PL, Hung J, Robinson JS, Lloyd BL (1987) Differences in left ventricular function between anterior and inferior myocardial infarction of equivalent enzymatic size. Int J Cardiol 17:155–167

    Article  PubMed  CAS  Google Scholar 

  29. Rakhit RD, Seiler C, Wustmann K, Zbinden S, Windecker S, Meier B, Eberli FR (2005) Tumour necrosis factor-alpha and interleukin-6 release during primary percutaneous coronary intervention for acute myocardial infarction is related to coronary collateral flow. Coron Artery Dis 16:147–152

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Third Department of Cardiology, Silesian Center for Heart Disease, Silesian Medical University, Szpitalna 2, 41-800, Zabrze, Poland

    Janusz Szkodzinski, Bartosz Hudzik, Bozena Szygula-Jurkiewicz & Lech Polonski

  2. Cardiology Ward, Sosnowiec, Poland

    Marcin Osuch

  3. Department of Internal Diseases, Silesian Medical University, Bytom, Poland

    Wojciech Romanowski & Barbara Zubelewicz-Szkodzinska

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  1. Janusz Szkodzinski
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  2. Bartosz Hudzik
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Correspondence to Janusz Szkodzinski.

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Szkodzinski, J., Hudzik, B., Osuch, M. et al. Serum concentrations of interleukin-4 and interferon-gamma in relation to severe left ventricular dysfunction in patients with acute myocardial infarction undergoing percutaneous coronary intervention. Heart Vessels 26, 399–407 (2011). https://doi.org/10.1007/s00380-010-0076-2

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