The role of IL-1 in the pathogenesis of heart disease



Interleukin (IL)-1 consists of two distinct ligands, IL-1α and IL-1β, with indistinguishable biological activities that signal through the IL-1 type I receptor (IL-1RI). A naturally occurring IL-1 receptor antagonist (IL-1Ra) binds to IL-1RI without initiating signal transduction and prevents IL-1 signaling, competitively inhibiting IL-1-mediated responses. Emerging evidence suggests that the balance between IL-1 agonists and antagonists plays an essential role in a variety of cardiovascular conditions. IL-1 may play a role in atherothrombotic disease by promoting the formation of atheromatous lesions, enhancing vascular inflammation, and triggering plaque destabilization. Following myocardial infarction, IL-1 critically regulates the inflammatory response and is involved in the development of adverse remodeling by enhancing expression of matrix metalloproteinases. IL-1 signaling may also be an essential mediator in the pathogenesis of heart failure by suppressing cardiac contractility, promoting myocardial hypertrophy, and inducing cardiomyocyte apoptosis. The present review summarizes current available data showing the significant role of IL-1 signaling in heart disease and raising the possibility that IL-1 inhibitors (such as anakinra, a nonglycosylated recombinant human IL-1Ra) may be clinically useful agents in patients with certain cardiovascular conditions.


interleukin-1 myocardial ischemia cardiac fibrosis hypertrophy remodeling inflammation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abbate A, Salloum FN, Vecile E et al (2008) Anakinra, a recombinant human interleukin-1 receptor antagonist, inhibits apoptosis in experimental acute myocardial infarction. Circulation 117: 2670–2683PubMedCrossRefGoogle Scholar
  2. Allan SM, Tyrrell PJ, Rothwell NJ (2005) Interleukin-1 and neuronal injury. Nat Rev Immunol 5: 629–640PubMedCrossRefGoogle Scholar
  3. Andrei C, Dazzi C, Lotti L et al (1999) The secretory route of the leaderless protein interleukin 1beta involves exocytosis of endolysosome-related vesicles. Mol Biol Cell 10: 1463–1475PubMedGoogle Scholar
  4. Apostolakis S, Vogiatzi K, Krambovitis E et al (2008) IL-1 cytokines in cardiovascular disease: diagnostic, prognostic and therapeutic implications. Cardiovasc Hematol Agents Med Chem 6: 150–158PubMedCrossRefGoogle Scholar
  5. Auron PE, Webb AC, Rosenwasser LJ et al (1984) Nucleotide sequence of human monocyte interleukin 1 precursor cDNA.. Proc Natl Acad Sci USA 81: 7907–7911PubMedCrossRefGoogle Scholar
  6. Barksby HE, Lea SR, Preshaw PM et al (2007) The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders. Clin Exp Immunol 149: 217–225PubMedCrossRefGoogle Scholar
  7. Berk BC, Fujiwara K, Lehoux S (2007) ECM remodeling in hypertensive heart disease. J Clin Invest 117: 568–575PubMedCrossRefGoogle Scholar
  8. Bevilacqua MP, Pober JS, Majeau GR et al (1984) Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med 160: 618–623PubMedCrossRefGoogle Scholar
  9. Bevilacqua MP, Pober JS, Wheeler ME et al (1985a) Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest 76: 2003–2011PubMedCrossRefGoogle Scholar
  10. Bevilacqua MP, Pober JS, Wheeler ME et al (1985b) Interleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion. Am J Pathol 121: 394–403Google Scholar
  11. Bonetti A, Marchini M, Ortolani F (2008) Immunolocalization of interleukin-1 receptor antagonist in healthy and infarcted myocardium. Histol Histopathol 23: 1093–1102PubMedGoogle Scholar
  12. Bujak M, Dobaczewski M, Chatila K et al (2008a) Interleukin1 receptor type I signaling critically regulates infarct healing and cardiac remodeling. Am J Pathol 173: 57–67PubMedCrossRefGoogle Scholar
  13. Bujak M, Frangogiannis NG (2007) The role of TGF-beta signaling in myocardial infarction and cardiac remodeling.. Cardiovasc Res 74: 184–195PubMedCrossRefGoogle Scholar
  14. Bujak M, Kweon HJ, Chatila K et al (2008) Aging-related defects are associated with adverse cardiac remodeling in a mouse model of reperfused myocardial infarction. J Am Coll Cardiol 51: 1384–1392PubMedCrossRefGoogle Scholar
  15. Bujak M, Ren G, Kweon HJ et al (2007) Essential role of Smad3 in infarct healing and in the pathogenesis of cardiac remodeling. Circulation 116: 2127–2138PubMedCrossRefGoogle Scholar
  16. 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: 569–582Google Scholar
  17. Colotta F, Dower SK, Sims JE et al (1994) The type II ‘decoy’ receptor: a novel regulatory pathway for interleukin 1.. Immunol Today 15: 562–566PubMedCrossRefGoogle Scholar
  18. Colotta F, Re F, Muzio MK et al (1993) Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4.. Science 261: 472–475PubMedCrossRefGoogle Scholar
  19. Colotta F, Re F, Polentarutti N et al (1992) Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. Blood 80: 2012–2020PubMedGoogle Scholar
  20. Coxon A, Bolon B, Estrada J (2002) Inhibition of interleukin1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis.. Arthritis Rheum 46: 2604–2612PubMedCrossRefGoogle Scholar
  21. Cozzolino F, Torcia M, Aldinucci D et al (1990) Interleukin 1 is an autocrine regulator of human endothelial cell growth.. Proc Natl Acad Sci USA 87: 6487–6491PubMedCrossRefGoogle Scholar
  22. Crossman DC, Morton AC, Gunn JP et al (2008) Investigation of the effect of Interleukin-1 receptor antagonist (IL-1ra) on markers of inflammation in non-ST elevation acute coronary syndromes (The MRC-ILA-HEART Study). Trials 9: 8PubMedCrossRefGoogle Scholar
  23. Deten A, Volz HC, Briest W et al (2002) Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats. Cardiovasc Res 55: 329–340Google Scholar
  24. Devlin CM, Kuriakose G, Hirsch E et al (2002) Genetic alterations of IL-1 receptor antagonist in mice affect plasma cholesterol level and foam cell lesion size. Proc Natl Acad Sci USA 99: 6280–6285PubMedCrossRefGoogle Scholar
  25. Dewald O, Ren G, Duerr GD et al (2004) Of mice and dogs: species-specific differences in the inflammatory response following myocardial infarction. Am J Pathol 164: 665–677PubMedGoogle Scholar
  26. Dinarello CA (1996) Biologic basis for interleukin-1 in disease.. Blood 87: 2095–2147PubMedGoogle Scholar
  27. Dinarello CA (1999) Cytokines as endogenous pyrogens.. J Infect Dis, 179(Suppl 2): S294–304CrossRefGoogle Scholar
  28. Dinarello CA (2000) The role of the interleukin-1-receptor antagonist in blocking inflammation mediated by interleukin-1.. N Engl J Med 343: 732–734PubMedCrossRefGoogle Scholar
  29. Dinarello CA (2007) Interleukin-18 and the pathogenesis of inflammatory diseases. Semin Nephrol 27: 98–114PubMedCrossRefGoogle Scholar
  30. Dobaczewski M, Bujak M, Zymek P et al (2006) Extracellular matrix remodeling in canine and mouse myocardial infarcts.. Cell Tissue Res 324: 475–488PubMedCrossRefGoogle Scholar
  31. Elhage R, Maret A, Pieraggi MT (1998) Differential effects of interleukin-1 receptor antagonist and tumor necrosis factor binding protein on fatty-streak formation in apolipoprotein E-deficient mice. Circulation 97: 242–244PubMedGoogle Scholar
  32. Eriksson U, Kurrer MO, Sonderegger I et al (2003) Activation of dendritic cells through the interleukin 1 receptor 1 is critical for the induction of autoimmune myocarditis. J Exp Med 197: 323–331PubMedCrossRefGoogle Scholar
  33. Fearon WF, Fearon DT (2008) Inflammation and cardiovascular disease: role of the interleukin-1 receptor antagonist.. Circulation 117: 2577–2579PubMedCrossRefGoogle Scholar
  34. Francis SE, Camp NJ, Dewberry RM et al (1999) Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease. Circulation 99: 861–866PubMedGoogle Scholar
  35. Frangogiannis NG (2007) Chemokines in ischemia and reperfusion. Thromb Haemost 97: 738–747PubMedGoogle Scholar
  36. Frangogiannis NG (2008) The immune system and cardiac repair. Pharmacol Res 58: 88–111PubMedCrossRefGoogle Scholar
  37. Frangogiannis NG, Mendoza LH, Lindsey ML et al (2000) IL10 is induced in the reperfused myocardium and may modulate the reaction to injury. J Immunol 165: 2798–2808PubMedGoogle Scholar
  38. Frangogiannis NG, Ren G, Dewald O et al (2005) The critical role of endogenous Thrombospondin (TSP)-1 in preventing expansion of healing myocardial infarcts. Circulation 111: 2935–2942PubMedCrossRefGoogle Scholar
  39. Giri JG, Wells J, Dower SK (1994) Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses. J Immunol 153: 5802–5809PubMedGoogle Scholar
  40. Guillen I, Blanes M, Gomez-Lechon MJ et al (1995) Cytokine signaling during myocardial infarction: sequential appearance of IL-1 beta and IL-6. Am J Physiol 269: R229–235PubMedGoogle Scholar
  41. Gulick T, Chung MK, Pieper SJ et al (1989) Interleukin 1 and tumor necrosis factor inhibit cardiac myocyte beta-adrenergic responsiveness. Proc Natl Acad Sci USA 86: 6753–6757PubMedCrossRefGoogle Scholar
  42. Gurantz D, Cowling RT, Varki N et al (2005) IL-1beta and TNF-alpha upregulate angiotensin II type 1 (AT1) receptors on cardiac fibroblasts and are associated with increased AT1 density in the post-MI heart. J Mol Cell Cardiol 38: 505–515PubMedCrossRefGoogle Scholar
  43. Hakkert BC, Kuijpers TW, Leeuwenberg JF et al (1991) Neutrophil and monocyte adherence to and migration across monolayers of cytokine-activated endothelial cells: the contribution of CD18, ELAM-1, and VLA-4. Blood 78: 2721–2726PubMedGoogle Scholar
  44. Han RO, Ray PE, Baughman KL et al (1991) Detection of interleukin and interleukin-receptor mRNA in human heart by polymerase chain reaction. Biochem Biophys Res Commun 181: 520–523PubMedCrossRefGoogle Scholar
  45. Herskowitz A, Choi S, Ansari AA et al (1995) Cytokine mRNA expression in postischemic/reperfused myocardium.. Am J Pathol 146: 419–428PubMedGoogle Scholar
  46. Horai R, Saijo S, Tanioka H (2000) Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J Exp Med 191: 313–320PubMedCrossRefGoogle Scholar
  47. Hu DE, Hori Y, Presta M et al (1994) Inhibition of angiogenesis in rats by IL-1 receptor antagonist and selected cytokine antibodies. Inflammation 18: 45–58PubMedCrossRefGoogle Scholar
  48. Huebener P, Abou-Khamis T, Zymek P et al (2008) CD44 is critically involved in infarct healing by regulating the inflammatory and fibrotic response. J Immunol 180: 2625–2633PubMedGoogle Scholar
  49. Huising MO, Stet RJ, Savelkoul HF et al (2004) The molecular evolution of the interleukin-1 family of cytokines; IL-18 in teleost fish. Dev Comp Immunol 28: 395–413PubMedCrossRefGoogle Scholar
  50. Hwang MW, Matsumori A, Furukawa Y et al (2001) Neutralization of interleukin-1beta in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling. J Am Coll Cardiol 38: 1546–1553PubMedCrossRefGoogle Scholar
  51. Iacoviello L, Di Castelnuovo A, Gattone M (2005) Polymorphisms of the interleukin-1beta gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro.. Arterioscler Thromb Vasc Biol 25: 222–227PubMedGoogle Scholar
  52. Ikonomidis I, Lekakis JP, Nikolaou M et al (2008) Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis.. Circulation 117: 2662–2669PubMedCrossRefGoogle Scholar
  53. Ing DJ, Zang J, Dzau VJ et al (1999) Modulation of cytokine-induced cardiac myocyte apoptosis by nitric oxide, Bak, and Bcl-x. Circ Res 84: 21–33PubMedGoogle Scholar
  54. Isoda K, Ohsuzu F (2006) The effect of interleukin-1 receptor antagonist on arteries and cholesterol metabolism.. J Atheroscler Thromb 13: 21–30PubMedGoogle Scholar
  55. Isoda K, Sawada S, Ayaori M et al (2005) Deficiency of interleukin-1 receptor antagonist deteriorates fatty liver and cholesterol metabolism in hypercholesterolemic mice. J Biol Chem 280: 7002–7009PubMedCrossRefGoogle Scholar
  56. Isoda K, Sawada S, Ishigami N et al (2004) Lack of interleukin-1 receptor antagonist modulates plaque composition in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 24: 1068–1073PubMedCrossRefGoogle Scholar
  57. Isoda K, Shiigai M, Ishigami N et al (2003) Deficiency of interleukin-1 receptor antagonist promotes neointimal formation after injury. Circulation 108: 516–518PubMedCrossRefGoogle Scholar
  58. Kastrati A, Koch W, Berger PB et al (2000) Protective role against restenosis from an interleukin-1 receptor antagonist gene polymorphism in patients treated with coronary stenting.. J Am Coll Cardiol 36: 2168–2173PubMedCrossRefGoogle Scholar
  59. Kleemann R, Zadelaar S, Kooistra T (2008) Cytokines and atherosclerosis: a comprehensive review of studies in mice.. Cardiovasc Res 79: 360–376PubMedCrossRefGoogle Scholar
  60. Koudssi F, Lopez JE, Villegas S et al (1998) Cardiac fibroblasts arrest at the G1/S restriction point in response to interleukin (IL)-1beta. Evidence for IL- 1(eta-induced hypophosphorylation of the retinoblastoma protein. J Biol Chem 273): 25796–25803Google Scholar
  61. Kumar A, Thota V, Dee L et al (1996) Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum. J Exp Med 183: 949–958PubMedCrossRefGoogle Scholar
  62. Kurrelmeyer KM, Michael LH, Baumgarten G et al (2000) Endogenous tumor necrosis factor protects the adult cardiac myocyte against ischemic-induced apoptosis in a murine model of acute myocardial infarction. Proc Natl Acad Sci USA 97: 5456–5461PubMedCrossRefGoogle Scholar
  63. Lane JR, Neumann DA, Lafond-Walker A et al (1993) Role of IL-1 and tumor necrosis factor in coxsackie virus-induced autoimmune myocarditis. J Immunol 151: 1682–1690PubMedGoogle Scholar
  64. Latini R, Bianchi M, Correale E et al (1994) Cytokines in acute myocardial infarction: selective increase in circulating tumor necrosis factor, its soluble receptor, and interleukin-1 receptor antagonist. J Cardiovasc Pharmacol 23: 1–6PubMedCrossRefGoogle Scholar
  65. Lee E, Grodzinsky AJ, Libby P et al (1995) Human vascular smooth muscle cell-monocyte interactions and metalloproteinase secretion in culture. Arterioscler Thromb Vasc Biol 15: 2284–2289PubMedGoogle Scholar
  66. Libby P, Sukhova G, Lee RT et al (1995) Cytokines regulate vascular functions related to stability of the atherosclerotic plaque. J Cardiovasc Pharmacol, 25 Suppl 2: S9–12CrossRefGoogle Scholar
  67. Libby P, Warner SJ, Friedman GB (1988) Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J Clin Invest 81: 487–498PubMedCrossRefGoogle Scholar
  68. Lim BK, Choe SC, Shin JO et al (2002) Local expression of interleukin-1 receptor antagonist by plasmid DNA improves mortality and decreases myocardial inflammation in experimental coxsackieviral myocarditis. Circulation 105: 1278–1281PubMedGoogle Scholar
  69. Liu H, Hanawa H, Yoshida T et al (2005) Effect of hydrodynamics-based gene delivery of plasmid DNA encoding interleukin-1 receptor antagonist-Ig for treatment of rat autoimmune myocarditis: possible mechanism for lymphocytes and noncardiac cells. Circulation 111: 1593–1600PubMedCrossRefGoogle Scholar
  70. Lomedico PT, Gubler U, Hellmann CP et al (1984) Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. Nature 312: 458–462PubMedCrossRefGoogle Scholar
  71. Mann DL (2005) Targeted anticytokine therapy and the failing heart. Am J Cardiol, 95:9C-16C; discussion 38C–40CGoogle Scholar
  72. Mantovani A, Locati M, Vecchi A et al (2001) Decoy receptors: a strategy to regulate inflammatory cytokines and chemokines. Trends Immunol 22: 328–336PubMedCrossRefGoogle Scholar
  73. March CJ, Mosley B, Larsen A et al (1985) Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature 315: 641–647PubMedCrossRefGoogle Scholar
  74. Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10: 417–426PubMedCrossRefGoogle Scholar
  75. Marui N, Offermann MK, Swerlick R et al (1993) Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest 92: 1866–1874PubMedCrossRefGoogle Scholar
  76. Maruyama K, Mori Y, Murasawa S et al (1999) Interleukin-1 beta upregulates cardiac expression of vascular endothelial growth factor and its receptor KDR/flk-1 via activation of protein tyrosine kinases. J Mol Cell Cardiol 31: 607–617PubMedCrossRefGoogle Scholar
  77. Matsushima K, Oppenheim JJ (1989) Interleukin 8 and MCAF: novel inflammatory cytokines inducible by IL 1 and TNF. Cytokine 1: 2–13PubMedCrossRefGoogle Scholar
  78. Mitchell MD, Laird RE, Brown RD et al (2007) IL-1beta stimulates rat cardiac fibroblast migration via MAP kinase pathways. Am J Physiol Heart Circ Physiol 292: H1139–1147PubMedCrossRefGoogle Scholar
  79. Mountain DJ, Singh M, Menon B et al (2007) Interleukin-1beta increases expression and activity of matrix metalloproteinase-2 in cardiac microvascular endothelial cells: role of PKCalpha/beta1 and MAPKs. Am J Physiol Cell Physiol 292: C867–875PubMedCrossRefGoogle Scholar
  80. Munkvad S, Gram J, Jespersen J (1991) Interleukin-1 and tumor necrosis factor-alpha in plasma of patients with acute ischemic heart disease who undergo thrombolytic therapy: a randomized, placebo-controlled study. Lymphokine Cytokine Res 10: 325–327PubMedGoogle Scholar
  81. Murtuza B, Suzuki K, Bou-Gharios G et al (2004) Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium. Proc Natl Acad Sci USA 101: 4216–4221PubMedCrossRefGoogle Scholar
  82. Nakano M, Knowlton AA, Dibbs Z et al (1998) Tumor necrosis factor-alpha confers esistance to hypoxic injury in the adult mammalian cardiac myocyte. Circulation 97: 1392–1400PubMedGoogle Scholar
  83. Neumann DA, Lane JR, Allen GS et al (1993) Viral myocarditis leading to cardiomyopathy: do cytokines contribute to pathogenesis. Clin Immunol Immunopathol 68: 181–190PubMedCrossRefGoogle Scholar
  84. Nicklin MJ, Hughes DE, Barton JL et al (2000) Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene. J Exp Med 191: 303–312PubMedCrossRefGoogle Scholar
  85. Nishikawa K, Yoshida M, Kusuhara M (2006) Left ventricular hypertrophy in mice with a cardiac-specific overexpression of interleukin-1. Am J Physiol Heart Circ Physiol 291: H176–183PubMedCrossRefGoogle Scholar
  86. Okamura H, Tsutsi H, Komatsu T et al (1995) Cloning of a new cytokine that induces IFN-gamma production by T cells.. Nature 378: 88–91PubMedCrossRefGoogle Scholar
  87. Opie LH, Commerford PJ, Gersh BJ et al (2006) Controversies in ventricular remodelling. Lancet 367: 356–367PubMedCrossRefGoogle Scholar
  88. Palmer JN, Hartogensis WE, Patten M et al (1995) Interleukin-1 beta induces cardiac myocyte growth but inhibits cardiac fibroblast proliferation in culture. J Clin Invest 95: 2555–2564PubMedCrossRefGoogle Scholar
  89. Patti G, D’Ambrosio A, Mega S et al (2004) Early interleukin-1 receptor antagonist elevation in patients with acute myocardial infarction. J Am Coll Cardiol 43: 35–38PubMedCrossRefGoogle Scholar
  90. Patti G, Mega S, Pasceri V et al (2005) Interleukin-1 receptor antagonist levels correlate with extent of myocardial loss in patients with acute myocardial infarction. Clin Cardiol 28: 193–196PubMedCrossRefGoogle Scholar
  91. Pfeffer MA, Braunwald E (1990) Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation 81: 1161–1172Google Scholar
  92. Raines EW, Dower SK, Ross R (1989) Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. Science 243: 393–396PubMedCrossRefGoogle Scholar
  93. Rectenwald JE, Moldawer LL, Huber TS et al (2000) Direct evidence for cytokine involvement in neointimal hyperplasia.. Circulation 102: 1697–1702PubMedGoogle Scholar
  94. Ren G, Michael LH, Entman ML et al (2002) Morphological characteristics of the microvasculature in healing myocardial infarcts. J Histochem Cytochem 50: 71–79PubMedGoogle Scholar
  95. Romero LI, Zhang DN, Herron GS et al (1997) Interleukin-1 induces major phenotypic changes in human skin microvascular endothelial cells. J Cell Physiol 173: 84–92PubMedCrossRefGoogle Scholar
  96. Schmitz J, Owyang A, Oldham E et al (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines.. Immunity 23: 479–490PubMedCrossRefGoogle Scholar
  97. Schreck R, Rieber P, Baeuerle PA (1991) Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1.. Embo J 10: 2247–2258PubMedGoogle Scholar
  98. Schulz R, Panas DL, Catena R et al (1995) The role of nitric oxide in cardiac depression induced by interleukin-1 beta and tumour necrosis factor-alpha. Br J Pharmacol 114: 27–34PubMedGoogle Scholar
  99. Shibata M, Endo S, Inada K et al (1997) Elevated plasma levels of interleukin-1 receptor antagonist and interleukin-10 in patients with acute myocardial infarction. J Interferon Cytokine Res 17: 145–150PubMedCrossRefGoogle Scholar
  100. Shioi T, Matsumori A, Kihara Y et al (1997) 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 81: 664–671PubMedGoogle Scholar
  101. Shioi T, Matsumori A, Sasayama S (1996) Persistent expression of cytokine in the chronic stage of viral myocarditis in mice. Circulation 94: 2930–2937PubMedGoogle Scholar
  102. Sica A, Matsushima K, Van Damme J (1990) IL-1 transcriptionally activates the neutrophil chemotactic factor/IL-8 gene in endothelial cells. Immunology 69: 548–553PubMedGoogle Scholar
  103. Sica A, Wang JM, Colotta F et al (1990) Monocyte chemotactic and activating factor gene expression induced in endothelial cells by IL-1 and tumor necrosis factor. J Immunol 144: 3034–3038PubMedGoogle Scholar
  104. Sims JE, Nicklin MJ, Bazan JF et al (2001) A new nomenclature for IL-1-family genes. Trends Immunol 22: 536–537PubMedCrossRefGoogle Scholar
  105. Siwik DA, Chang DL, Colucci WS (2000) Interleukin-1beta and tumor necrosis factor-alpha decrease collagen synthesis and increase matrix metalloproteinase activity in cardiac fibroblasts in vitro. Circ Res 86: 1259–1265PubMedGoogle Scholar
  106. StJohn Sutton M, Pfeffer MA, Plappert T et al (1994) Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril. Circulation 89: 68–75Google Scholar
  107. Suzuki K, Murtuza B, Smolenski RT et al (2001) Overexpression of interleukin-1 receptor antagonist provides cardioprotection against ischemia-reperfusion injuryGoogle Scholar
  108. associated with reduction in apoptosis. Circulation 104:I308–I303Google Scholar
  109. Tavazzi L (1999) Clinical epidemiology of acute myocardial infarction. Am Heart J 138: S48–54PubMedCrossRefGoogle Scholar
  110. Thaik CM, Calderone A, Takahashi N et al (1995) Interleukin-1 beta modulates the growth and phenotype of neonatal rat cardiac myocytes. J Clin Invest 96: 1093–1099PubMedCrossRefGoogle Scholar
  111. Thornberry NA, Bull HG, Calaycay JR et al (1992) A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356: 768–774PubMedCrossRefGoogle Scholar
  112. Ushio S, Namba M, Okura T et al (1996) Cloning of the cDNA for human IFN-gamma-inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein. J Immunol 156: 4274–4279PubMedGoogle Scholar
  113. Vanderheyden M, Paulus WJ, Voss M et al (2005) Myocardial cytokine gene expression is higher in aortic stenosis than in idiopathic dilated cardiomyopathy. Heart 91: 926–931PubMedCrossRefGoogle Scholar
  114. van Minkelen R, Wettinger SB, de Visser MC et al (2009) Haplotypes of the interleukin-1 receptor antagonist gene, interleukin-1 receptor antagonist mRNA levels and the risk of myocardial infarction. Atherosclerosis 203: 201–205PubMedCrossRefGoogle Scholar
  115. Wang X, Romanic AM, Yue TL et al (2000) Expression of interleukin-1beta, interleukin-1 receptor, and interleukin-1 receptor antagonist mRNA in rat carotid artery after balloon angioplasty. Biochem Biophys Res Commun 271: 138–143PubMedCrossRefGoogle Scholar
  116. White HD, Norris RM, Brown MA et al (1987) Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 76: 44–51PubMedGoogle Scholar
  117. Xia Y, Lee K, Li N et al (2009) Characterization of the inflammatory and fibrotic response in a mouse model of cardiac pressure overload. Histochem Cell Biol 131: 471–481PubMedCrossRefGoogle Scholar
  118. Zee RY, Fernandez-Ortiz A, Macaya C et al (2003) IL-1 cluster genes and occurrence of post-percutaneous transluminal coronary angioplasty restenosis: a prospective, angiography-based evaluation. Atherosclerosis 171: 259–264PubMedCrossRefGoogle Scholar
  119. Zee RY, Hennessey H, Michaud SE et al (2009) Genetic variants within the interleukin-1 gene cluster, and risk of incident myocardial infarction, and ischemic stroke: A nested case-control approach. Atherosclerosis (in press)Google Scholar
  120. Zymek P, Bujak M, Chatila K et al (2006) The role of platelet-derived growth factor signaling in healing myocardial infarcts.. J Am Coll Cardiol 48: 2315–2323PubMedCrossRefGoogle Scholar
  121. Zymek P, Nah DY, Bujak M et al (2007) Interleukin-10 is not a critical regulator of infarct healing and left ventricular remodeling. Cardiovasc Res 74: 313–322PubMedCrossRefGoogle Scholar

Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2009

Authors and Affiliations

  1. 1.Section of Cardiovascular SciencesBaylor College of MedicineHoustonUSA

Personalised recommendations