Skip to main content
SpringerLink
Log in

Role of inflammation in the progression of heart failure

  • Management of Heart Failure
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Chronic heart failure (HF) is a disorder characterized in part by immune activation and inflammation. Thus, patients with HF have elevated levels of a number of inflammatory cytokines, both in the circulation and in the failing heart itself. Several mechanisms for this immune activation, which are not mutually exclusive, have been suggested, including neurohormonal activation, hemodynamic overload, and activation of the innate immune system secondary to cardiac stress. Importantly, experimental studies have shown that inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and monocyte chemoattractant peptide-1 may contribute to the development and progression of HF by promoting myocardial hypertrophy, activating matrix metalloproteinases, provoking contractile dysfunction, and inducing apoptosis. However, inflammatory cytokines may also have adaptive and cardioprotective effects. This important aspect of cytokine biology must be kept in mind when designing new immunomodulatory treatment modalities in HF.

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

Similar content being viewed by others

References and Recommended Reading

  1. McMurray J, Pfeffer MA:New therapeutic options in congestive heart failure: Part I.Circulation 2002,105:2099–2106.

    Article  PubMed  Google Scholar 

  2. Levine B, Kalman J, Mayer L, et al.:Elevated circulating levels of tumor necrosis factor in severe chronic heart failure.N Engl J Med 1990,323:236–241.

    PubMed  CAS  Google Scholar 

  3. Mann DL:Inflammatory mediators and the failing heart: Past, present, and the foreseeable future.Circ Res 2002,91:988–998.

    Article  PubMed  CAS  Google Scholar 

  4. Aukrust P, Ueland T, Lien E, et al.:Cytokine network in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.Am J Cardiol 1999,83:376–382.

    Article  PubMed  CAS  Google Scholar 

  5. Torre-Amione G, Kapadia S, Benedict C, et al.:Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the studies of left ventricular dysfunction (SOLVD).J Am Coll Cardiol 1996,27:1201–1206.

    Article  PubMed  CAS  Google Scholar 

  6. Mallat Z, Heymes C, Corbaz A, et al.:Evidence for altered interleukin 18 (IL)-18 pathway in human heart failure.FASEB J 2004,18:1752–1754.

    PubMed  CAS  Google Scholar 

  7. Aukrust P, Ueland T, Müller F, et al.:Elevated circulating levels of C-C chemokines in patients with congestive heart failure.Circulation 1998,97:1136–1143.

    PubMed  CAS  Google Scholar 

  8. Damås JK, Gullestad L, Ueland T, et al.:CXC-chemokines, a new group of cytokines in congestive heart failure-possible role of platelets and monocytes.Cardiovasc Res 2000,45:428–436.

    Article  PubMed  Google Scholar 

  9. Damås JK, Gullestad L, Aass H, et al.:Enhanced gene expression of chemokines and their corresponding receptors in mononuclear blood cells in chronic heart failure-modulatory effect of intravenous immunoglobulin.J Am Coll Cardiol 2001,38:187–193.

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  11. Eiken HG, Øie E, Damås JK, et al.:Myocardial gene expression of leukaemia inhibitory factor, interleukin-6 and glycoprotein 130 in end-stage human heart failure.Eur J Clin Invest 2001,31:389–397.

    Article  PubMed  CAS  Google Scholar 

  12. Prabhu SD, Chandrasekar B, Murray DR, Freeman GL:Beta-adrenergic blockade in developing heart failure: effects on myocardial inflammatory cytokines, nitric oxide, and remodeling.Circulation 2000,101:2103–2109.

    PubMed  CAS  Google Scholar 

  13. Wei GC, Sirois MG, Qu R, et al.:Subacute and chronic effects of quinapril on cardiac cytokine expression, remodeling, and function after myocardial infarction in the rat.J Cardiovasc Pharmacol 2002,39:842–850.

    Article  PubMed  CAS  Google Scholar 

  14. Brasier AR, Recinos A 3rd, Eledrisi MS:Vascular inflammation and the renin-angiotensin system.Arterioscler Thromb Vasc Biol 2002,22:1257–1266.

    Article  PubMed  CAS  Google Scholar 

  15. Werner C, Werdan K, Ponicke K, Brodde OE:Impaired beta-adrenergic control of immune function in patients with chronic heart failure: reversal by beta1-blocker treatment.Basic Res Cardiol 2001,96:290–298.

    Article  PubMed  CAS  Google Scholar 

  16. Of importance Jankowska EA, Ponikowski P, Piepoli MF, et al.:Autonomic imbalance and immune activation in chronic heart failure — pathophysiological links.Cardiovasc Res 2006,70:434–445. Elegant review discussing neurohormonal activation and in particular autonomic imbalance as causes of immune activation in HF.

    Article  PubMed  CAS  Google Scholar 

  17. Shioi T, Matsumori A, Kihara Y, et al.:Increased expression of interleukin-1 beta and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the hypertrophied and failing heart with pressure overload.Circ Res 1997,81:664–671.

    PubMed  CAS  Google Scholar 

  18. Singal PK, Khaper N, Palace V, Kumar D:The role of oxidative stress in the genesis of heart disease.Cardiovasc Res 1998,40:426–432.

    Article  PubMed  CAS  Google Scholar 

  19. Knuefermann P, Vallejo J, Mann DL:The role of innate immune responses in the heart in health and disease.Trends Cardiovasc Med 2004,14:1–7.

    Article  PubMed  Google Scholar 

  20. Satoh M, Shimoda Y, Maesawa C, et al.:Activated toll-like receptor 4 in monocytes is associated with heart failure after acute myocardial infarction.Int J Cardiol 2005,109:226–234.

    Article  PubMed  Google Scholar 

  21. Eriksson U, Ricci R, Hunziker L, et al.:Dendritic cell-induced autoimmune heart failure requires cooperation between adaptive and innate immunity.Nat Med 2003,9:1484–1490.

    Article  PubMed  CAS  Google Scholar 

  22. Dunzendorfer S, Lee HK, Soldau K, Tobias PS:Toll-like receptor 4 functions intracellularly in human coronary artery endothelial cells: roles of LBP and sCD14 in mediating LPS responses.FASEB J 2004,18:1117–1119.

    PubMed  CAS  Google Scholar 

  23. Ha T, Li Y, Hua F, et al.:Reduced cardiac hypertrophy in toll-like receptor 4-deficient mice following pressure overload.Cardiovasc Res 2005,68:224–234.

    Article  PubMed  CAS  Google Scholar 

  24. Penninger JM, Bachmaier K:Review of microbial infections and the immune response to cardiac antigens.J Infect Dis 2000,181(Suppl 3):S498-S504.

    Article  PubMed  CAS  Google Scholar 

  25. Niebauer J, Volk H-D, Kemp M, et al.:Endotoxin and immune activation in chronic heart failure: a prospective cohort study.Lancet 1999,353:1838–1842.

    Article  PubMed  CAS  Google Scholar 

  26. Conraads VM, Jorens PG, De Clerck LS, et al.:Selective intestinal decontamination in advanced chronic heart failure: a pilot trial.Eur J Heart Fail 2004,6:483–491.

    Article  PubMed  CAS  Google Scholar 

  27. Yndestad A, Holm AM, Müller F, et al.:Enhanced expression of inflammatory cytokines and activation markers in T-cells from patients with chronic heart failure.Cardiovasc Res 2003,60:141–146.

    Article  PubMed  CAS  Google Scholar 

  28. Kruger S, Kunz D, Graf J, et al.:Endotoxin hypersensitivity in chronic heart failure.Int J Cardiol 2007,115:159–163.

    Article  PubMed  Google Scholar 

  29. Of major importance Hilfiker-Kleiner D, Landmesser U, Drexler H:Molecular mechanisms in heart failure: focus on cardiac hypertrophy, inflammation, angiogenesis, and apoptosis.J Am Coll Cardiol 2006,48:A56-A66. Review that includes discussion of cardioprotective effects of gp130 signaling and role of apoptosis in HF.

    Article  CAS  Google Scholar 

  30. Palmer JN, Hartogensis WE, Patten M, et al.:Interleukn-1 beta induces cardiac myocyte growth but inhibits cardiac fibroblast proliferation in culture.J Clin Invest 1995,95:2555–2564.

    Article  PubMed  CAS  Google Scholar 

  31. Nishikawa K, Yoshida M, Kusuhara M, et al.:Left ventricular hypertrophy in mice with a cardiac-specific overexpression of interleukin-1.Am J Physiol Heart Circ Physiol 2006,291:H176-H183.

    Article  PubMed  CAS  Google Scholar 

  32. Chandrasekar B, Mummidi S, Claycomb WC, et al.:Interleukin-18 is a pro-hypertrophic cytokine that acts through a phosphatidylinositol 3-kinase-phosphoinositide-dependent kinase-1-Akt-GATA4 signaling pathway in cardiomyocytes.J Biol Chem 2005,280:4553–4567.

    Article  PubMed  CAS  Google Scholar 

  33. Woldbaek PR, Sande JB, Stromme TA, et al.:Daily administration of interleukin-18 causes myocardial dysfunction in healthy mice.Am J Physiol Heart Circ Physiol 2005,289: H708-H714.

    Article  PubMed  CAS  Google Scholar 

  34. Of major importance Wilson EM, Diwan A, Spinale FG, Mann DL:Duality of innate stress responses in cardiac injury, repair, and remodeling.J Mol Cell Cardiol 2004,37:801–811. Insightful review of adaptive and maladaptive effects of innate immune responses and inflammation in cardiac remodeling.

    Article  PubMed  CAS  Google Scholar 

  35. Flesch M, Hoper A, Dell’Italia L, et al.:Activation and functional significance of the renin-angiotensin system in mice with cardiac restricted overexpression of tumor necrosis factor.Circulation 2003,108:598–604.

    Article  PubMed  CAS  Google Scholar 

  36. Singh M, Ananthula S, Milhorn DM, et al.:Osteopontin: A novel inflammatory mediator of cardiovascular disease.Front Biosci 2007,12:214–221.

    Article  PubMed  CAS  Google Scholar 

  37. Kawano S, Kubota T, Monden Y, et al.:Blockade of NF-kappaB ameliorates myocardial hypertrophy in response to chronic infusion of angiotensin II.Cardiovasc Res 2005,67:689–698.

    Article  PubMed  CAS  Google Scholar 

  38. Of importance Rutschow S, Li J, Schultheiss HP, Pauschinger M:Myocardial proteases and matrix remodeling in inflammatory heart disease.Cardiovasc Res 2006,69:646–656. Review of inflammation and regulation of MMPs and extracellular matrix turnover in HF.

    Article  PubMed  CAS  Google Scholar 

  39. Bradham WS, Bozkurt B, Gunasinghe H, et al.:Tumor necrosis factor-alpha and myocardial remodeling in progression of heart failure: a current perspective.Cardiovasc Res 2002,53:822–830.

    Article  PubMed  CAS  Google Scholar 

  40. Gurantz D, Yndestad A, Halvorsen B, et al.:Etanercept or intravenous immunoglobulin attenuates expression of genes involved in post-myocardial infarction remodeling.Cardiovasc Res 2005,67:106–115.

    Article  PubMed  CAS  Google Scholar 

  41. Siwik DA, Chang DL-F, Colucci WS:Interleukin-1beta and tumor necrosis factor-alpha decrease collagen synthesis and increase matrix metalloproteinase activity in cardiac fibroblasts in vitro.Circ Res 2000,86:1259–1265.

    PubMed  CAS  Google Scholar 

  42. Wang F, Trial J, Diwan A, et al.:Regulation of cardiac fibroblast cellular function by leukemia inhibitory factor.J Mol Cell Cardiol 2002,34:1309–1316.

    Article  PubMed  CAS  Google Scholar 

  43. Ueland T, Yndestad A, Øie E, et al.:Dysregulated osteoprotegerin/RANK ligand/RANK axis in clinical and experimental heart failure.Circulation 2005,111:2461–2468.

    Article  PubMed  CAS  Google Scholar 

  44. Aggarwal BB:Signaling pathways of the TNF superfamily: a double-edged sword.Nat Rev Immunol 2003,3:745–756.

    Article  PubMed  CAS  Google Scholar 

  45. Kumar A, Haery C, Parrillo JE:Myocardial dysfunction in septic shock.Crit Care Clin 2000,16:251–287.

    Article  PubMed  CAS  Google Scholar 

  46. Of major importance Prabhu SD:Cytokine-induced modulation of cardiac function.Circ Res 2004,95:1140–1153. Extensive review of effects on modulation of cardiac function by inflammatory cytokines.

    Article  PubMed  CAS  Google Scholar 

  47. Bozkurt B, Kribbs SB, Clubb FJ Jr, et al.:Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive left ventricular dysfunction and remodeling in rats.Circulation 1998,97:1382–1391.

    PubMed  CAS  Google Scholar 

  48. Florholmen G, Aas V, Rustan AC, et al.:Leukemia inhibitory factor reduces contractile function and induces alterations in energy metabolism in isolated cardiomyocytes.J Mol Cell Cardiol 2004,37:1183–1193.

    Article  PubMed  CAS  Google Scholar 

  49. Kang KM, Izumo S:Apoptosis in heart: basic mechanisms and implications in cardiovascular diseases.Trends Mol Med 2003,9:177–182.

    Article  PubMed  CAS  Google Scholar 

  50. Kaur K, Sharma AK, Dhingra S, Singal PK:Interplay of TNF-alpha and IL-10 in regulating oxidative stress in isolated adult cardiac myocytes.J Mol Cell Cardiol 2006,41:1023–1030.

    Article  PubMed  CAS  Google Scholar 

  51. Hirota H, Chen J, Betz UA, et al.:Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress.Cell 1999,97:189–198.

    Article  PubMed  CAS  Google Scholar 

  52. Of importance Morimoto H, Takahashi M, Izawa A, et al.:Cardiac overexpression of monocyte chemoattractant protein-1 in transgenic mice prevents cardiac dysfunction and remodeling after myocardial infarction.Circ Res 2006,99:891–899. Study demonstrating potential cardioprotective effects of MCP-1.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Clinical Immunology and Infectious Diseases, Medical Department, Rikshospitalet-Radiumhospitalet Medical Center, Sognsvannsveien 20, N-0027, Oslo, Norway

    Pål Aukrust MD, PhD

Authors
  1. Arne Yndestad PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jan Kristian Damås MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erik Øie MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thor Ueland PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lars Gullestad MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pål Aukrust MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pål Aukrust MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yndestad, A., Damås, J.K., Øie, E. et al. Role of inflammation in the progression of heart failure. Curr Cardiol Rep 9, 236–241 (2007). https://doi.org/10.1007/BF02938356

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02938356

Keywords

Search

Navigation