Skip to main content
SpringerLink
Log in

Therapeutic Potential of Anticytokine Therapy in Congestive Heart Failure

  • Review Article
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Accumulating evidence indicates that inflammatory cytokines play a pathogenic role in congestive heart failure (CHF) by influencing heart contractility, inducing hypertrophy, and promoting apoptosis or fibrosis, contributing to the continuous myocardial remodeling process. While several stimuli may be operating such as heat-shock protein, microbial antigen, bacterial lipopolysaccharide, shear and oxidative stress, hypoxia and oxidized low-density lipoprotein (LDL), it seems that the inflammatory response to these stimuli may represent a common final pathogenic pathway in CHF regardless of the initial event. Traditional cardiovascular drugs seem to have little influence on the overall cytokine network, and immunomudulatory therapy has emerged as a possible new treatment modality in CHF. Several animal studies, and some clinical pilot studies, have suggested that down-regulation of inflammatory cytokines may improve cardiac performance. On the other hand, preliminary results from the placebo-controlled studies suggest no effect, or even adverse effect, of antitumor necrosis factor (TNF) therapy on mortality and hospitalization. Although somewhat disappointing, these negative results do not necessarily argue against the ’cytokine hypothesis‘. These studies just underscore the difficulties and the challenges in developing treatment modalities that can modulate the cytokine network in CHF patients resulting in anti-inflammatory and beneficial net effects. Further research in this area will have to more precisely identify the most important actors in the immunopathogenesis of CHF in order to develop more specific immunomodulating agents for this disorder. However, at present the beneficial role of anticytokine therapy in patients with CHF remains unproven.

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
Table I
Fig. 3

Similar content being viewed by others

References

  1. Levine B, Kaiman J, Mayer L, et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 1990; 323: 236–41

    Article  PubMed  CAS  Google Scholar 

  2. 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: 376–82

    Article  PubMed  CAS  Google Scholar 

  3. Testa M, Yeh M, Lee P, et al. Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension. J Am Coll Cardiol 1996; 28: 964–71

    Article  PubMed  CAS  Google Scholar 

  4. 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: 1201–6

    Article  PubMed  CAS  Google Scholar 

  5. Munger MA, Johnson B, Amber IJ, et al. Circulating concentrations of proinflammatory cytokines in mild or moderate heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1996; 77: 423–7

    Article  Google Scholar 

  6. Yamaoka-Tojo M, Tojo T, Inomata T, et al. Circulating levels of interleukin 18 reflect etiologies of heart failure: Th1/Th2 cytokine imbalance exaggerates the pathophysiology of advanced heart failure. J Card Fail 2002; 8: 21–7

    Article  PubMed  CAS  Google Scholar 

  7. Aukrust P, Ueland T, Muller F, et al. Elevated circulating levels of C-C chemokines in patients with congestive heart failure. Circulation 1998; 97: 1136–43

    Article  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: 428–36

    Article  PubMed  Google Scholar 

  9. Aukrust P, Gullestad L, Lappegård KT, et al. Complement activation in patients with congestive heart failure: effect of high-dose intravenous immunoglobulin treatment. Circulation 2001; 104: 1494–500

    Article  PubMed  CAS  Google Scholar 

  10. 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 effects of intravenous immunoglobulin. J Am Coll Cardiol 2001; 38: 187–93

    Article  PubMed  Google Scholar 

  11. Torre-Amione G, Kapadia S, Lee J, et al. Tumor necrosis factor-α and tumor necrosis factor receptors in the failing human heart. Circulation 1996; 93: 704–11

    Article  PubMed  CAS  Google Scholar 

  12. Deveaux B, Scholz D, Hirche A, et al. Upregulation of cell adhesion molecules and the presence of low grade inflammation in human chronic heart failure. Eur Heart J 1997; 18:470–9

    Article  Google Scholar 

  13. Damås JK, Eiken HG, Øie E, et al. Myocardial expression of CC- and CXC-chemokines and their receptors in human end-stage heart failure. Cardiovasc Res 2000; 47: 778–87

    Article  PubMed  Google Scholar 

  14. Eiken HG, Øie E, Damås JK, et al. Myocardial gene expression of leukemia inhibitory factor, interleukin-6 and glycoprotein 130 in end-stage human heart failure. Eur J Clin Invest 2001; 31: 389–97

    Article  PubMed  CAS  Google Scholar 

  15. Deswal A, Petersen NJ, Feldman AM, et al. Cytokines and cytokine receptors in advanced heart failure. Circulation 2001; 103: 2055–9

    Article  PubMed  CAS  Google Scholar 

  16. Becker AE, de Boer OJ, van Der Wal AC. The role of inflammation and infection in coronary artery disease. Annu Rev Med 2001; 52: 289–97

    Article  PubMed  CAS  Google Scholar 

  17. Bachmaier K, Neu N, de la Maza, et al. Chlamydia infections and heart disease linked through antigenic mimicry. Science 1999; 283: 1335-9

    Article  PubMed  CAS  Google Scholar 

  18. Gauntt CJ, Arizpe HM, Higdon AL, et al. Molecular mimicry, anti-coxsackievirus B3 neutralizing monoclonal antibodies, and myocarditis. J Immunol 1995; 154: 2983–95

    PubMed  CAS  Google Scholar 

  19. Niebauer J, Volk H-D, Kemp M, et al. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet 1999; 353: 1838–42

    Article  PubMed  CAS  Google Scholar 

  20. Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2001; 2: 675–80

    Article  PubMed  CAS  Google Scholar 

  21. Dybdahl B, Wahba A, Lien E, et al. Inflammatory response after open heart surgery: release of heat-shock protein 70 and signaling through toll-like receptor-4. Circulation 2002; 105: 685–90

    Article  PubMed  CAS  Google Scholar 

  22. Frantz S, Kobzik L, Kim YD, et al. Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest 1999; 104: 271–80

    Article  PubMed  CAS  Google Scholar 

  23. Nemoto S, Vallejo JG, Knuefermann P. Escherichia coli LPS-induced LV dysfunction: role of toll-like receptor-4 in the adult heart. Am J Physiol Heart Circ Physiol 2002; 282: H2316–23

    PubMed  CAS  Google Scholar 

  24. Kiechl S, Lorenz E, Reindl M, et al. Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med 2002; 347: 185–92

    Article  PubMed  CAS  Google Scholar 

  25. Frantz S, Kelly RA, Bourcier T. Role of TLR-2 in the activation of nuclear factor kappaB by oxidative stress in cardiac myocytes. J Biol Chem 2001; 276: 5197–203

    Article  PubMed  CAS  Google Scholar 

  26. Okada M, Matsumori A, Ono K, et al. Cyclic stretch upregulates production of interleukin-8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human endothelial cells. Arterioscler Thromb Vasc Biol 1998; 18: 894–901

    Article  PubMed  CAS  Google Scholar 

  27. Shioi T, Matsumori A, Kihara Y, et al. Increased expression of interleukin-1 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the hypertrophied and failing heart with pressure overload. Circ Res 1997; 81: 664–71

    Article  PubMed  CAS  Google Scholar 

  28. Singal PK, Khaper N, Palace V, et al. The role of oxidative stress in the genesis of heart disease. Cardiovasc Res 1998; 40: 426–32

    Article  PubMed  CAS  Google Scholar 

  29. Baumgarten G, Knuefermann P, Kalra D, et al. Load-dependent and -independent regulation of proinflammatory cytokine and cytokine receptor gene expression in the adult mammalian heart. Circulation 2002; 105: 2192–7

    Article  PubMed  CAS  Google Scholar 

  30. Janabi M, Yamashita S, Hirano K, et al. Oxidized LDL-induced NF-kappa B activation and subsequent expression of proinflammatory genes are defective in monocyte-derived macrophages from CD36-deficient patients. Arterioscler Thromb Vasc Biol 2000; 20: 1953–60

    Article  PubMed  CAS  Google Scholar 

  31. Holm T, Damås JK, Holven K, et al. CXC-chemokines in coronary artery disease: possible pathogenic role of interactions between oxidized-LDL, platelets and peripheral blood mononuclear cells. J Thromb Haemost 2003; 1(2): 257–62

    Article  PubMed  CAS  Google Scholar 

  32. Blum A, Miller H. Pathophysiological role of cytokines in congestive heart failure Annu Rev Med 2001; 52: 15–27

    Article  PubMed  CAS  Google Scholar 

  33. Meldrum DR. Tumor necrosis factor in the heart. Am J Physiol 1998; 274: R577–95

    PubMed  CAS  Google Scholar 

  34. Feldman AM, Combes A, Wagner D, et al. The role of tumor necrosis factor in the pathophysiology of heart failure. J Am Coll Cardiol 2000; 35: 537–44

    Article  PubMed  CAS  Google Scholar 

  35. Kubota T, McTernan CF, Frye CS, et al. Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ Res 1997; 81: 627–35

    Article  PubMed  CAS  Google Scholar 

  36. Bozkurt B, Kribbs SB, Clubb FJ, et al. Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive dysfunction and remodelling in rats. Circulation 1998; 97: 1382–91

    Article  PubMed  CAS  Google Scholar 

  37. 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: 822–30

    Article  PubMed  CAS  Google Scholar 

  38. Sivasubramanian N, Coker ML, Kurrelmeyer KM, et al. Left ventricular remodeling in transgenic mice with cardiac restricted overexpression of tumor necrosis factor. Circulation 2001; 104: 826–31

    Article  PubMed  CAS  Google Scholar 

  39. Yaniv G, Shilkrut M, Lotan R, et al. Hypoxia predisposes neonatal rat ventricular myocytes to apoptosis induced by activation of the Fas (CD95/Apo-1) receptor: Fas activation and apoptosis in hypoxic myocytes. Cardiovasc Res 2002; 54: 611–23

    Article  PubMed  CAS  Google Scholar 

  40. Nakamura T, Ueda Y, Juan Y, et al. Fas-Mediated apoptosis in adriamycin-induced cardiomyopathy in rats: in vivo study. Circulation 2000; 102: 572–8

    Article  PubMed  CAS  Google Scholar 

  41. Yndestad A, Damås JK, Eiken HG, et al. Increased gene expression of tumor necrosis factor superfamily ligands in peripheral blood mononuclear cells during chronic heart failure. Cardiovasc Res 2002; 54: 175–82

    Article  PubMed  CAS  Google Scholar 

  42. Nelson DP, Setser E, Hall DG, et al. Proinflammatory consequences of transgenic fas ligand expression in the heart. J Clin Invest 2000; 105: 1199–208

    Article  PubMed  CAS  Google Scholar 

  43. Badorff C, Ruetten H, Mueller S, et al. Fas receptor signaling inhibits glycogen synthase kinase 3 beta and induces cardiac hypertrophy following pressure overload. J Clin Invest 2002; 109: 373–81

    PubMed  CAS  Google Scholar 

  44. Kunisada K, Tone E, Fujio Y, et al. Activation of gpl30 transduces hypertrophic signals via STAT3 in cardiac myocytes. Circulation 1998; 98: 346–52

    Article  PubMed  CAS  Google Scholar 

  45. Kodama H, Fukuda K, Pan J, et al. Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, activates the JAK/ST AT pathway in rat cardiomyocytes. Circ Res 1997; 81: 656–63

    Article  PubMed  CAS  Google Scholar 

  46. Wollert KC, Taga T, Saito M, et al. Cardiotrophin-1 activates a distinct form of cardiac muscle cell hypertrophy: assembly of sarcomeric units in series VIA gp130/leukemia inhibitory factor receptor-dependent pathways. J Biol Chem 1996; 271: 9535–45

    Article  PubMed  CAS  Google Scholar 

  47. Hirota H, Yoshida K, Kishimoto T, et al. Continuous activation of gp130, a signaltransducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice. Proc Natl Acad Sci U S A 1995; 92: 4862–6

    Article  PubMed  CAS  Google Scholar 

  48. Kunisada K, Negoro S, Tone E, et al. Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophie signal but a protective signal against doxorubicin-induced cardiomyopathy. Proc Natl Acad Sci U S A 2000; 97: 315–9

    Article  PubMed  CAS  Google Scholar 

  49. 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: 189–98

    Article  PubMed  CAS  Google Scholar 

  50. Sasayama S, Okada M, Matsumori A. Chemokines and cardiovascular diseases. Cardiovasc Res 2000; 45: 267–9

    Article  PubMed  CAS  Google Scholar 

  51. Kolattukudy PE, Quasch T, Berges S. Myocarditis induced by targeted expression of the MCP-1 gene in murine cardiac muscle. Am J Pathol 1998; 152: 101–11

    PubMed  CAS  Google Scholar 

  52. Cook DN, Beck MA, Coffman TM, et al. Requirement of MIP-1 alpha for an inflammatory response to viral infection. Science 1995; 269: 1583–5

    Article  PubMed  CAS  Google Scholar 

  53. Tachibana K, Hirota S, Ilzasa H, et al. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature 1998; 393: 524–5

    Article  Google Scholar 

  54. Matsumori A, Ono K, Nishio R, et al. Amiodarone inhibits production of tumor necrosis factor-alpha by human mononuclear cells: a possible mechanism for its effect in heart failure. Circulation 1997; 96: 1386–9

    Article  PubMed  CAS  Google Scholar 

  55. Manna SK, Aggarwal BB. Vesnarinone suppresses TNF-induced activation of NF-kappa B, c-Jun kinase, and apoptosis. J Immunol 2000; 164: 5815–25

    PubMed  CAS  Google Scholar 

  56. Oral H, Fisher SG, Fay WP, et al. Effects of amiodarone on tumor necrosis factor-alpha levels in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1999; 83: 388–91

    Article  PubMed  CAS  Google Scholar 

  57. Mohler ER, Sorensen LC, Ghali JK, et al. Role of cytokines in the mechanism of action of amlodipine: The PRAISE Heart Failure Trial. J Am Coll Cardiol 1997; 30: 35–41

    Article  PubMed  CAS  Google Scholar 

  58. Gullestad L, Aukrust P, Ueland T, et al. Effect of high-versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure. J Am Coll Cardiol 1999; 34: 2061–7

    Article  PubMed  CAS  Google Scholar 

  59. Pan J, Fukuda K, Kodama H, et al. Role of angiotensin II in activation of the JAK/ STAT pathway induced by acute pressure overload in the rat heart. Circ Res 1997; 81: 611–7

    Article  PubMed  CAS  Google Scholar 

  60. Swedberg K, Held P, Kjekshus J, et al. Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction: results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II). N Engl J Med 1992; 327: 678–84

    Article  PubMed  CAS  Google Scholar 

  61. Hernandez-Presa M, Bustos C, Ortega M, et al. Angiotensin-converting enzyme inhibition prevents arterial factor-kappa B activation, monocyte chemoattractant protein-1 expression, and macrophage infiltration in a rabbit model of accelerated atherosclerosis. Circulation 1997; 95: 1532–41

    Article  PubMed  CAS  Google Scholar 

  62. Soejima H, Ogawa H, Yasue H, et al. Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction. J Am Coll Cardiol 1999; 34: 983–8

    Article  PubMed  CAS  Google Scholar 

  63. Yu CM, Tipoe GL, Lai KWH, et al. Effects of combination of angiotensinconverting enzyme inhibitor and angiotensin receptor antagonist on inflammatory cellular infiltration and myocardial fibrosis after acute myocardial infarction. J Am Coll Cardiol 2001; 38: 1207–15

    Article  PubMed  CAS  Google Scholar 

  64. Maisel AS, Murray D, Lotz M, et al. Propranolol treatment affects parameters of human immunity. Immunopharmacology 1991; 22: 157–64

    Article  PubMed  CAS  Google Scholar 

  65. Ohtsuka T, Hamada M, Hiasa G, et al. Effects of beta-blockers on circulating levels of inflammatory and anti-inflammatory cytokines in patients with dilated cardiomyopathy. J Am Coll Cardiol 2001; 37: 412–7

    Article  PubMed  CAS  Google Scholar 

  66. Gullestad L, Ueland T, Brunsvig A, et al. Effect of β-blockade on cytokine levels in chronic heart failure-a substudy in the MERIT-HF trial. Am Heart J 2001; 141: 418–21

    Article  PubMed  CAS  Google Scholar 

  67. Matsumura T, Tsushima K, Ohtaki E, et al. Effects of carvedilol on plasma levels of interleukin-6 and tumor necrosis factor-alpha in nine patients with dilated cardiomyopathy. J Cardiol 2002; 39: 253–7

    PubMed  Google Scholar 

  68. Deswal A, Bozkurt B, Seta Y, et al. Safety and efficacy of a soluble p75 tumor necrosis factor receptor (Enbrel, Etanercept) in patients with advanced heart failure. Circulation 1999; 99: 3224–6

    Article  PubMed  CAS  Google Scholar 

  69. Anker SD, Coats AJS. How to recover from RENAISSANCE? The significance of the results from of RECOVER, RENAISSANCE, RENEWAL and ATTACH. Int J Cardiol 2002; 86: 123–30

    Article  PubMed  Google Scholar 

  70. Lisman KA, Stetson SJ, Koerner MM, et al. The role of tumor necrosis factor alpha blockade in the treatment of congestive heart failure. Congest Heart Fail 2002; 8: 275–9

    Article  PubMed  CAS  Google Scholar 

  71. Kadokami T, McTiernan CF, Kubota T, et al. Effects of soluble TNF receptor treatment on lipopolysaccharide-induced myocardial cytokine expression. Am J Physiol 2001; 280: H2281–91

    CAS  Google Scholar 

  72. Lügering A, Schmidt M, Lügering N, et al. Infliximab induces apoptosis in monocytes from patients with chronic active Crohn’s Disease by using a caspase-dependent pathway. Gastroenterology 2001; 121: 1145–57

    Article  PubMed  Google Scholar 

  73. Abraham E. Why immunomodulatory therapies have not worked in sepsis. Intensive Care Med 1999; 25: 556–66

    Article  PubMed  CAS  Google Scholar 

  74. Sliwa K, Skudicky D, Candy G, et al. Randomized investigation of effects of pentoxifylline on left ventricular performance in idiopathic dilated cardiomyopathy. Lancet 1998; 351: 1091–3

    Article  PubMed  CAS  Google Scholar 

  75. Skudicky D, Bergmann A, Sliwa K, et al. Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol. Circulation 2001; 103: 1083–8

    Article  PubMed  CAS  Google Scholar 

  76. Davey PP, Ashrafian H. New therapies for heart failure: is thalidomide the answer? QJM 2000; 93: 305–11

    Article  PubMed  CAS  Google Scholar 

  77. Adlard JW. Thalidomide in the treatment of cancer. Anticancer Drugs 2000; 11: 787–91

    Article  PubMed  CAS  Google Scholar 

  78. Gullestad L, Semb AG, Holt E, et al. Effect of thalidomide in patients with chronic heart failure. Am Heart J 2002; 144: 847–50

    PubMed  CAS  Google Scholar 

  79. Haslett PA, Corral LG, Albert M, et al. Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med 1998; 187: 1885–92

    Article  PubMed  CAS  Google Scholar 

  80. Haslett PA, Klausner JD, Makonkawkeyoon S, et al. Thalidomide stimulates T cell responses and interleukin 12 production in HIV-infected patients AIDS Res Hum Retroviruses 1999; 15: 1169–79

    Article  CAS  Google Scholar 

  81. Felix SB, Staudt A, Friedrich GB. Improvement of cardiac function after immunoadsorption in patients with dilated cardiomyopathy. Autoimmunity 2001; 34: 211–5

    Article  PubMed  CAS  Google Scholar 

  82. Felix SB, Staudt A, Landsberger M, et al. Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption. J Am Coll Cardiol 2002; 39: 646–52

    Article  PubMed  CAS  Google Scholar 

  83. Staudt A, Schaper F, Stangl V, et al. Immunohistological changes in dilated cardiomyopathy induced by immunoadsorption therapy and subsequent immunoglobulin substitution. Circulation 2001; 103: 2681–6

    Article  PubMed  CAS  Google Scholar 

  84. Scandinavian Simvastatin Survival Study Group. Randomizes trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–9

    Google Scholar 

  85. The Long-Term Intervention with Pravastatin in ischaemic disease (LIPID) study group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339: 1349–57

    Article  Google Scholar 

  86. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333: 1301–7

    Article  PubMed  CAS  Google Scholar 

  87. Kwak B, Mulhaupt F, Mylt S, et al. Statins as a newly recognized type of immunomodulator. Nat Med 2000; 6: 1399–402

    Article  PubMed  CAS  Google Scholar 

  88. Laufs U, Kilter H, Konkol C, et al. Impact of HMG CoA reductase inhibition on small GTPases in the heart. Cardiovasc Res 2002; 53: 911–20

    Article  PubMed  CAS  Google Scholar 

  89. Hayashidani S, Tsutsui H, Shiomi T, et al. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation 2002; 105: 868–73

    Article  PubMed  CAS  Google Scholar 

  90. Takemoto M, Node K, Nakagami H, et al. Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy. J Clin Invest 2001; 108: 1429–37

    PubMed  CAS  Google Scholar 

  91. Krum H, McMurray JJ. Statins and chronic heart failure: do we need a large-scale outcome trial? J Am Coll Cardiol 2002; 39: 1567–73

    Article  PubMed  CAS  Google Scholar 

  92. Holm T, Andreassen AK, Ueland T, et al. Effect of Pravastatin on plasma markers of inflammation and peripheral endothelial function in male heart transplant recipients. Am J Cardiol 2001; 87: 815–8

    Article  PubMed  CAS  Google Scholar 

  93. Kiener PA, Davis PM, Murray JL, et al. Stimulation of inflammatory responses in vitro and in vivo by lipophilic HMG-CoA reductase inhibitors. Int J Immunopharmacol 2001; 1: 105–18

    Article  CAS  Google Scholar 

  94. Ballow M. Mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory diseases. J Allergy Clin Immunol 1997; 100: 151–7

    Article  PubMed  CAS  Google Scholar 

  95. Mobini N, Sarela A, Ahmed AR. Intravenous immunoglobins in the therapy of autoimmune and systemic inflammatory disorders. Ann Allergy Asthma Immunol 1995; 74: 107–6

    Google Scholar 

  96. McNamara DM, Rosenblum WD, Janosko KM, et al. Intravenous immune globulin in the therapy of myocarditis and acute cardiomyopathy. Circulation 1997; 95: 2476–8

    Article  PubMed  CAS  Google Scholar 

  97. Bozkurt B, Villaneuva FS, Holubkov R, et al. Intravenous immune globulin in the therapy of peripartum cardiomyopathy. J Am Coll Cardiol 1999; 34: 177–80

    Article  PubMed  CAS  Google Scholar 

  98. Gullestad L, Aass H, Fjeld JG, et al. Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure. Circulation 2001; 103: 220–5

    Article  PubMed  CAS  Google Scholar 

  99. Wolf HM, Eibl MM. Immunomodulatory effect of immunoglobulins. Clin Exp Rheumatol 1996; 14 Suppl. 15: S17–25

    PubMed  Google Scholar 

  100. Vassilev TL, Kazatchkine MD, Van Juyen J-P, et al. Inhibition of cell adhesion by antibodies to Arg-Gly-Asp (RGD) in normal immunoglobulin for therapeutic use (intravenous immunoglobulin, IVIg). Blood 1999; 93: 3624–31

    PubMed  CAS  Google Scholar 

  101. Viard I, Wehrli P, Bullani R, et al. Inhibition of toxic necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science 1998; 282: 490–3

    Article  PubMed  CAS  Google Scholar 

  102. Anderson U, Bjork L, Skansen-Saphir U, et al. Pooled human IgG modulates cytokine production in lymphocytes and monocytes. Immunol Rev 1994; 139: 21–42

    Article  Google Scholar 

  103. Aukrust P, Frøland SS, Liabakk NB, et al. Release of cytokines, soluble cytokine receptors and interleukin-1 receptor antagonist after intravenous immunoglobulin administration in vivo. Blood 1994; 84: 2136–43

    PubMed  CAS  Google Scholar 

  104. Aukrust P, Damås JK, Gullestad L, et al. Chemokines in myocardial failure: pathogenic importance and potential therapeutic targets. Clin Exp Immunol 2001; 124:343–5

    Article  PubMed  CAS  Google Scholar 

  105. McNamara DM, Holubkov R, Starling RC, et al. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation 2001; 103: 2254–9

    Article  PubMed  CAS  Google Scholar 

  106. Mallat Z, Besnard S, Duriez M, et al. Protective role of interleukin-10 in atheroscleosis. Circ Res 1999; 85: 17–24

    Article  Google Scholar 

  107. Nishio R, Matsumori A, Shioi T, et al. Treatment of experimental viral myocarditis with interleukin-10. Circulation 1999; 100: 1102–8

    Article  PubMed  CAS  Google Scholar 

  108. Shito M, Wakabayashi G, Ueda M, et al. Interleukin 1 receptor blockade reduces tumor necrosis factor production, tissue injury, and mortality after hepatic ischemia-reperfusion in the rat. Transplantation 1997; 63: 143–8

    Article  PubMed  CAS  Google Scholar 

  109. Suzuki K, Murtuza B, Smolenski RT, et al. Overexpression of interleukin-1 receptor antagonist provides cardioprotection against ischemia-reperfusion injury associated with reduction in apoptosis. Circulation 2001; 104 (12 Suppl. 1): I308–I3

    PubMed  CAS  Google Scholar 

  110. Takano H, Nagai T, Asakawa M, et al. Peroxisome proliferator-activated receptor activators inhibit lipopolysaccharide-induced tumor necrosis factor-alpha expression in neonatal rat cardiac myocytes. Circ Res 2000; 87: 596–602

    Article  PubMed  CAS  Google Scholar 

  111. Hara M, Ono K, Hwang MW, et al. Evidence for a role of mast cells in the evolution to congestive heart failure J Exp Med 2002; 195: 375–81

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.

Author information

Authors and Affiliations

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

    Pal Aukrust

  2. Research Institute for Internal Medicine, Rikshospitalet, Oslo, Norway

    Pal Aukrust, Arne Yndestad & Jan K. Damås

  3. Department of Cardiology, Rikshospitalet, Oslo, Norway

    Jan K. Damås

  4. Department of Medicine, Bærum Hospital, Sandvika, Norway

    Lars Gullestad

Authors
  1. Pal Aukrust
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arne Yndestad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jan K. Damås
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lars Gullestad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pal Aukrust.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aukrust, P., Yndestad, A., Damås, J.K. et al. Therapeutic Potential of Anticytokine Therapy in Congestive Heart Failure. Am J Cardiovasc Drugs 4, 169–177 (2004). https://doi.org/10.2165/00129784-200404030-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00129784-200404030-00004

Keywords

Search

Navigation