Skip to main content

Advertisement

SpringerLink
Log in

Interleukin-6, -7, -8 and -10 predict outcome in acute myocardial infarction complicated by cardiogenic shock

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Background

The IABP-SHOCK-trial was a morbidity-based randomized controlled trial in patients with infarction-related cardiogenic shock (CS), which used the change of the quantified degree of multiorgan failure as determined by APACHE II score over a 4-day period as primary outcome measure. The prospective hypothesis was that adding IABP therapy to “standard care” would improve CS-triggered multi organ dysfunction syndrome (MODS). The primary endpoint showed no difference between conventionally managed cardiogenic shock patients and those with IABP support. In an inflammatory marker substudy, we analysed the prognostic value of interleukin (IL)-1β, -6, -7, -8, and -10 in patients with acute myocardial infarction complicated by cardiogenic shock.

Design

Inflammatory marker substudy of the prospective, randomized, controlled, open label IABP-SHOCK-trial (Clinical-Trials-gov-ID-NCT00469248).

Setting and methods

A single-center study was performed in a 12-bed Intensive-Care-Unit in an university hospital in which 40 consecutive patients were enrolled with an observational period of 96 h.

Results

The pro- and anti-inflammatory markers IL-6, -7, -8 and -10 showed a predictive power for mortality of infarct-related CS patients, while IL-1β did not discriminate. The maximal values during the observational period, in case of IL-7 the minimal value, showed the best power to predict mortality. Both, ROC and multivariate analyses confirmed these suggestions (area under the curve: IL-8, 0.80 ± 0.08; IL-6, 0.79 ± 0.08; IL-10, 0.76 ± 0.08; IL-7, 0.69 ± 0.08). Inflammatory markers were not affected by the presence of IABP support.

Conclusion

The inflammatory response in patients with myocardial infarction complicated by cardiogenic shock, as reflected by the inflammatory markers IL-6, IL-7, IL-8 and IL-10, demonstrates a clinically relevant prognostic contribution to clinical outcome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Prondzinsky R, Lemm H, Swyter M, Wegener N, Unverzagt S, Carter JM, Russ M, Schlitt A, Buerke U, Christoph A, Schmidt H, Winkler M, Thiery J, Werdan K, Buerke M (2010) Intra-aortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock: the prospective, randomized IABP SHOCK Trial for attenuation of multiorgan dysfunction syndrome. Crit Care Med 38:152–160

    Article  PubMed  CAS  Google Scholar 

  2. Hochman JS, Sleeper LA, Webb JG et al (1999) Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK investigators. Should we emergently revascularize occluded coronaries for cardiogenic shock. N Engl J Med 341:625–634

    Article  PubMed  CAS  Google Scholar 

  3. Ruiz-Bailen M, Rucabado-Aguilar L, Exposito-Ruiz M et al (2009) Cardiogenic shock in acute coronary syndrome. Med Sci Monit 15:RA57–RA66

    PubMed  Google Scholar 

  4. Kouraki K, Schneider S, Uebis R, Tebbe U, Klein HH, Janssens U, Zahn R, Senges J, Zeymer U (2011) Characteristics and clinical outcome of 458 patients with acute myocardial infarction requiring mechanical ventilation. Results of the BEAT registry of the ALKK-study group. Clin Res Cardiol 100(3):235–239

    Article  PubMed  Google Scholar 

  5. Liebetrau C, Szardien S, Rixe J, Woelken M, Rolf A, Bauer T, Nef H, Möllmann H, Hamm C, Weber M (2011) Direct admission versus transfer of AMI patients for primary PCI. Clin Res Cardiol 100(3):217–225

    Article  PubMed  Google Scholar 

  6. Mielniczuk LM, Pfeffer MA, Lewis EF, Blazing MA, de Lemos JA, Mohanavelu S, Rouleau J, Fox K, Pedersen TR, Califf RM (2009) Acute decline in renal function, inflammation, and cardiovascular risk after an acute coronary syndrome. Clin J Am Soc Nephrol 4:1811–1817

    Article  PubMed  CAS  Google Scholar 

  7. Tan J, Hua Q, Li J, Fan Z (2009) Prognostic value of interleukin-6 during a 3-year follow-up in patients with acute ST-segment elevation myocardial infarction. Heart Vessels 24:329–334

    Article  PubMed  Google Scholar 

  8. Järemo P, Nilsson O (2008) Interleukin-6 and neutrophils are associated with long-term survival after acute myocardial infarction. Eur J Intern Med 19:330–333

    Article  PubMed  Google Scholar 

  9. Debrunner M, Schuiki E, Minder E, Straumann E, Naegeli B, Mury R, Bertel O, Frielingsdorf J (2008) Proinflammatory cytokines in acute myocardial infarction with and without cardiogenic shock. Clin Res Cardiol 97:298–305

    Article  PubMed  CAS  Google Scholar 

  10. Geppert A, Steiner A, Zorn G, Delle-Karth G, Koreny M, Haumer M, Siostrzonek P, Huber K, Heinz G (2002) Multiple organ failure in patients with cardiogenic shock is associated with high plasma levels of interleukin-6. Crit Care Med 30:1987–1994

    Article  PubMed  CAS  Google Scholar 

  11. Kohsaka S, Menon V, Lowe AM, Lange M, Dzavik V, Sleeper LA, Hochman JS (2005) SHOCK Investigators. Systemic inflammatory response syndrome after acute myocardial infarction complicated by cardiogenic shock. Arch Intern Med 165:1643–1650

    Article  PubMed  Google Scholar 

  12. Lin WC, Lin CF, Chen CL, Chen CW, Lin YS (2010) Prediction of outcome in patients with acute respiratory distress syndrome by bronchoalveolar lavage inflammatory mediators. Exp Biol Med 235:57–65

    Article  CAS  Google Scholar 

  13. Prinsen JH, Baranski E, Posch H, Tober K, Gerstmeyer A (2008) Interleukin-6 as diagnostic marker for neonatal sepsis: determination of Access IL-6 cutoff for newborns. Clin Lab 54:179–183

    PubMed  Google Scholar 

  14. Witthaut R, Busch C, Fraunberger P, Walli A, Seidel D, Pilz G, Stuttmann R, Speichermann N, Verner L, Werdan K (2003) Plasma atrial natriuretic peptide and brain natriuretic peptide are increased in septic shock: impact of interleukin-6 and sepsis-associated left ventricular dysfunction. Intensive Care Med 29:1696–1702

    Article  PubMed  Google Scholar 

  15. Altman DA (1991) Practical statistics for medical research. Chapman & Hall, London

    Google Scholar 

  16. Sauerbrei W, Madjar H, Prömpeler HJ (1998) Differentiation of benign and malignant breast tumours by logistic regression and a classification tree using Doppler flow signals. Methods Inf Med 37:226–234

    PubMed  CAS  Google Scholar 

  17. Känel R, Carney RM, Zhao S, Whooley MA (2011) Heart rate variability and biomarkers of systemic inflammation in patients with stable coronary heart disease: findings from the Heart and Soul Study. Clin Res Cardiol 100(3):241–247

    Article  Google Scholar 

  18. Villar J, Maca-Meyer N, Pérez-Méndez L, Flores C (2004) Bench-to-bedside review: understanding genetic predisposition to sepsis. Crit Care 8:180–189

    Article  PubMed  Google Scholar 

  19. Fitting C, Cheval C, Losser MR, Carlet J, Payen D, Foster K, Cavaillon JM (1997) Presence of high levels of leukocyte-associated interleukin-8 upon cell activation and in patients with sepsis syndrome. Infect Immun 65:865–871

    PubMed  Google Scholar 

  20. Zeerleder S, Caliezi C, van Mierlo G, Eerenberg-Belmer A, Sulzer I, Hack CE, Wuillemin WA (2003) Clin Diagn Lab Immunol 10:529–535

    PubMed  CAS  Google Scholar 

  21. Mokart D, Merlin M, Sannini A, Brun JP, Delpero JR, Houvenaeghel G, Moutardier V, Blache JL (2005) Procalcitonin, interleukin 6 and systemic inflammatory response syndrome (SIRS): early markers of postoperative sepsis after major surgery. Br J Anaesth 94:767–773

    Article  PubMed  CAS  Google Scholar 

  22. Weber GF, Schlautkötter S, Kaiser-Moore S, Altmayr F, Holzmann B, Weighardt H (2007) Inhibition of interleukin-22 attenuates bacterial load and organ failure during acute polymicrobial sepsis. Infect Immun 75:1690–1697

    Article  PubMed  CAS  Google Scholar 

  23. Torre-Amnione Kapadia S, Lee J et al (1996) Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart. Circulation 93:704–711

    Google Scholar 

  24. Werra ID (1997) Cytokines, nitrite/nitrate, soluble tumor necrosis factro receptors, and procalcitonin concentrations: comparison in patients with septic shock, cardiogenic shock, and bacterial pneumonia. Crit Care Med 25:607–613

    Article  PubMed  Google Scholar 

  25. Neumann FJ, Ott I, Gawaz M et al (1995) Cardiac release of cytokines and inflammatory responses in acute myocardial infarction. Circulation 92:748–755

    PubMed  CAS  Google Scholar 

  26. Adrie C, Adib-Conquy M, Laurent I, Monchi M, Vinsonneau C, Fitting C, Fraisse F, Dinh-Xuan AT, Carli P, Spaulding C, Dhainaut JF, Cavaillon JM (2002) Successful cardiopulmonary resuscitation after cardiac arrest as a “sepsis-like” syndrome. Circulation 106:562–568

    Article  PubMed  Google Scholar 

  27. Kohsaka S, Menon V, Iwata K, Lowe A, Sleeper LA, Hochman JS (2007) SHOCK investigators. Microbiological profile of septic complication in patients with cardiogenic shock following acute myocardial infarction (from the SHOCK study). Am J Cardiol 99:802–804

    Article  PubMed  Google Scholar 

  28. Kadokami T, McTiernan C, Kubota T, Frye C, Bounoutas G, Robbins P, Watkins S, Feldman A (2001) Effects of soluble TNF receptor treatment on lipopolysaccharide-induced myocardial cytokine expression. Am J Physiol Heart Circ Physiol 280:H2281–H2291

    PubMed  CAS  Google Scholar 

  29. Miettinen JA, Ylitalo K, Hedberg P, Kervinen K, Niemelä M, Säily M, Koistinen P, Savolainen ER, Ukkonen H, Pietilä M, Airaksinen KE, Knuuti J, Vuolteenaho O, Mäkikallio TH, Huikuri HV (2011) Effects of intracoronary injection of autologous bone marrow-derived stem cells on natriuretic peptides and inflammatory markers in patients with acute ST-elevation myocardial infarction. Clin Res Cardiol 100(4):317–325

    Article  PubMed  CAS  Google Scholar 

  30. Prondzinsky R, Müller-Werdan U, Pilz G, Witthaut R, Stabenow I, Werdan K, Zerkowski HR (1997) Systemic inflammatory reactions to extracorporeal therapy measures (II): cardiopulmonary bypass. Wien Klin Wochenschr 109:346–353

    PubMed  CAS  Google Scholar 

  31. Prondzinsky R, Knüpfer A, Loppnow H, Redling F, Lehmann DW, Stabenow I, Witthaut R, Unverzagt S, Radke J, Zerkowski HR, Werdan K (2005) Surgical trauma affects the proinflammatory status after cardiac surgery to a higher degree than cardiopulmonary bypass. J Thorac Cardiovasc Surg 129:760–766

    Article  PubMed  Google Scholar 

  32. Kilger E, Heyn J, Beiras-Fernandez A, Luchting B, Weis F (2011) Stress doses of hydrocortisone reduce systemic inflammatory response in patients undergoing cardiac surgery without cardiopulmonary bypass. Minerva Anestesiol 77:268–274

    PubMed  CAS  Google Scholar 

  33. Steinvil A, Berliner S, Shapira I, Rogowski O, Justo D, George J, Halkin A, Keren G, Finkelstein A, Banai S, Arbel Y (2010) Time to rheology in acute myocardial infarction: inflammation and erythrocyte aggregation as a consequence and not necessarily as precursors of the disease. Clin Res Cardiol 99(10):651–656

    Article  PubMed  Google Scholar 

  34. Jung C, Rödiger C, Fritzenwanger M, Schumm J, Lauten A, Figulla HR, Ferrari M (2009) Acute microflow changes after stop and restart of intra-aortic balloon pump in cardiogenic shock. Clin Res Cardiol 98(8):469–475

    Article  PubMed  CAS  Google Scholar 

  35. Munsterman LD, Elbers PW, Ozdemir A, van Dongen EP, van Iterson M, Ince C (2010) Withdrawing intra-aortic balloon pump support paradoxically improves microvascular flow. Crit Care 14(4):R161

    Article  PubMed  Google Scholar 

  36. Osuchowski MF, Welch K, Siddiqui J, Remick DG (2006) Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality. J Immunol 177:1967–1974

    PubMed  CAS  Google Scholar 

  37. Schröder J, Kahlke V, Staubach KH, Zabel P, Stüber F (1998) Gender differences in human sepsis. Arch Surg 133:1200–1205

    Article  PubMed  Google Scholar 

  38. Arranz L, Lord JM, De la Fuente M (2010) Preserved ex vivo inflammatory status and cytokine responses in naturally long-lived mice. Age (Dordr) 32:451–466

    Article  CAS  Google Scholar 

  39. Agarwal S, Busse PJ (2010) Innate and adaptive immunosenescence. Ann Allergy Asthma Immunol 104:183–190

    Article  PubMed  CAS  Google Scholar 

  40. Wong CP, Magnusson KR, Ho E (2010) Aging is associated with altered dendritic cells subset distribution and impaired proinflammatory cytokine production. Exp Gerontol 45:163–169

    Article  PubMed  CAS  Google Scholar 

  41. Schmidt C, Höcherl K, Kurt B, Moritz S, Kurtz A, Bucher M (2010) Blockade of multiple but not single cytokines abrogates downregulation of angiotensin II type-I receptors and anticipates septic shock. Cytokine 49:30–38

    Article  PubMed  CAS  Google Scholar 

  42. Cha J, Wang Z, Ao L et al (2008) Cytokines link Toll-like receptor 4 signaling to cardiac dysfunction after global myocardial ischemia. Ann Thorac Surg 85:1678–1685

    Article  PubMed  Google Scholar 

  43. Katz JN, Stebbins AL, Alexander JH, Reynolds HR, Pieper KS, Ruzyllo W, Werdan K, Geppert A, Dzavik V, Van de Werf F, Hochman JS (2009) TRIUMPH investigators. Predictors of 30-day mortality in patients with refractory cardiogenic shock following acute myocardial infarction despite a patent infarct artery. Am Heart J 158:680–687

    Article  PubMed  Google Scholar 

  44. Youssef AA, Chang LT, Hang CL, Wu CJ, Cheng CI, Yang CH, Sheu JJ, Chai HT, Chua S, Yeh KH, Yip HK (2007) Level and value of interleukin-18 in patients with acute myocardial infarction undergoing primary coronary angioplasty. Circ J 71:703–708

    Article  PubMed  CAS  Google Scholar 

  45. Yamamoto T, Terajima K, Kato K, Iwasaki YK, Miyagi Y, Sato N, Takeda S, Tanaka K, Takano T (2006) Transient leukocytopenia associated with a steep surge of pro-inflammatory cytokines in a patient with severe cardiogenic pulmonary edema. Intern Med 45:1153–1155

    Article  PubMed  Google Scholar 

  46. Buerke M, Murohara T, Skurk C et al (1995) Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion. Proc Natl Acad Sci 92:8031–8035

    Article  PubMed  CAS  Google Scholar 

  47. Rupprecht HJ, vom Dahl J, Terres W et al (2000) Cardioprotective effects of the Na+/H+ exchange inhibitor cariporide in patients with acute anterior myocardial infarction undergoing direct PTCA. Circulation 101:2902–2908

    PubMed  CAS  Google Scholar 

  48. Werdan K, Pilz G, Bujdoso O et al (2007) Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study. Crit Care Med 35:2693–2701

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare the following relations: R.P., K.W., and M.B. received lecture fees from Datascope Inc. The IABP-Shock-Trial was supported by an unrestricted grant from Datascope Inc.

Author information

Author notes

  1. Roland Prondzinsky

    Present address: Department of Medicine I, Carl von Basedow Klinikum, Academic Teaching Hospital, Martin Luther-University Halle-Wittenberg, Weisse Mauer 52, 06217, Merseburg, Germany

Authors and Affiliations

  1. Department of Medicine III, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany

    Roland Prondzinsky, Henning Lemm, Nikolas-Arne Wegener, Axel Schlitt, Konstantin M. Heinroth, Sebastian Dietz, Ute Buerke, Patrick Kellner, Harald Loppnow, Karl Werdan & Michael Buerke

  2. Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany

    Susanne Unverzagt

  3. Department of Anaesthesiology, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany

    Patrick Kellner

  4. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany

    Martin G. Fiedler & Joachim Thiery

Authors
  1. Roland Prondzinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susanne Unverzagt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Henning Lemm
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nikolas-Arne Wegener
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Axel Schlitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Konstantin M. Heinroth
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sebastian Dietz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ute Buerke
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Patrick Kellner
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Harald Loppnow
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Martin G. Fiedler
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Joachim Thiery
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Karl Werdan
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Michael Buerke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roland Prondzinsky.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Prondzinsky, R., Unverzagt, S., Lemm, H. et al. Interleukin-6, -7, -8 and -10 predict outcome in acute myocardial infarction complicated by cardiogenic shock. Clin Res Cardiol 101, 375–384 (2012). https://doi.org/10.1007/s00392-011-0403-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-011-0403-3

Keywords

Search

Navigation