Chapter 10
Immunomodulating Therapy in Chronic Heart Failure
Lars Gullestad,
Jan Kristian Damås,
Arne Yndestad,
Pål Aukrust,
Lars Gullestad
Search for more papers by this authorJan Kristian Damås
Search for more papers by this authorArne Yndestad
Search for more papers by this authorPål Aukrust
Search for more papers by this authorLars Gullestad,
Jan Kristian Damås,
Arne Yndestad,
Pål Aukrust,
Lars Gullestad
Search for more papers by this authorJan Kristian Damås
Search for more papers by this authorArne Yndestad
Search for more papers by this authorPål Aukrust
Search for more papers by this authorBook Editor(s):Ronald Ross Watson,
Douglas F. Larson,
Ronald Ross Watson
Department of Nutritional Sciences, The University of Arizona; and Sarver Heart Center, College of Medicine, The University of Arizona
Division of Health Promotion Sciences, Mel and Enid Zuckerman Arizona College of Public Health, The University of Arizona Tucson, AZ USA
Search for more papers by this authorDouglas F. Larson
Sarver Heart Center College of Medicine The University of Arizona Tucson, AZ USA
Search for more papers by this authorFirst published: 30 August 2007
Summary
This chapter contains section titled:
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Overview
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Introduction
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Rationale for immunomodulating therapy
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Pathophysiological consequences of immune activation in HF
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Immunomodulating therapy
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Targeted anticytokine therapy
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Why did the anti-TNF therapy fail?
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Nonspecific immunomodulating therapy
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New therapeutic targets in HF
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Conclusions
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References
References
- Stewart S MacIntyre, K, MacLeod, MMC, Bailey, AM, Cap-well S McMurray J.J. Trends in hospitalization for Heart failure in Scotland, 1990–1996. Eur Heart J 2001; 22: 209–17.
- Cowie MR Mosterd A Wood D. et al. The epidemiology of Heart failure. Eur Heart J 1997; 18: 208–25.
- Aukrust, P, Ueland, T, Lien, E et al. Cytokine networkincon-gestive Heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1999; 83: 376–82.
- 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.
- Torre-Amione G Kapadia S Benedict C Oral H Young JB Mann D.L. Proinflammatorycytokinelevelsin 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.
- Kawakami H Shigematsu Y Ohtsuka T. Increased circulating soluble form of Fas in patients with dilated car-diomyopathy. Jpn Circ J 1998; 62: 873–6.
- 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.
- Damaås 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.
- Kapadia S. Cytokines and Heart failure. Cardiol Rev 1999; 7: 196–206.
- 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-modulatoryeffectsofintravenous immunoglobulin. J Am Coll Cardiol 2001; 38: 187–93.
- Deveaux B Scholz D Hirche A Kløverkorn WP Schaper J. Upregulation of cell adhesion molecules and the presence of low grade inflammation in human chronic Heart failure. Eur Heart J 1997; 18: 470–9.
- Damås, JK, Eiken, HG, øie, E et al. Myocardialexpression of CC- and CXC-chemokines and their receptors in human end-stage Heart failure. Cardiovasc Res 2000; 47: 778–87.
- Seta Y Shan K Bozkurt B Oral H Mann D.L. Basic mechanism in Heart failure: the cytokine hypothesis. J Cardiac Failure 1996; 2: 243–49.
- Deswal A Petersen, NJ, Feldman, AM, Young, JB, White, BG, Mann, D.L. Cytokines and cytokine receptors in advanced Heart failure. Circulation 2001; 103: 2055–9.
- Ueland T Kjekshus J Froland S. et al. Plasma levels of soluble tumor necrosis factor receptor type I during the acute phase following complicated myocardial infarction predicts survival in high-risk patients. J Am Coll Cardiol 2005; 46: 2018–21.
- Bozkurt B Kribbs SB Clubb F. et al. Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive dysfunction and remodellingin rats. Circulation 1998; 97: 1382–91.
- Kubota T McTernan CF Frye C. et al. Dilated car-diomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ Res 1997; 81: 627–35.
- Finkel MS Oddis CV Jacob TD Watkins SC Hattler BG Simmons R.L. Negative inotropic effects of cytokines on the Heart mediated by nitricoxide. Science 1992; 257: 387–9.
- Yokoyama T Vaca L Rossen RD Durante W Hazarika P Mann D.L. Cellular basis for the negative inotropic effects of tumornecrosisfactor-alpha in adult mammalian Heart. J Clin Invest 1993; 92: 2303–12.
- Krown KA Page MT Nguyen C et al. Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. J Clin Invest 1996; 98: 2854–65.
- Mann DL Lee-Jackson D Yokayama T. Tumor necrosis factor alpha and cardiac remodeling. Heart Fail 1995; 11: 166–76.
- Hirota H Chen J Betz A. et al. Loss of gp130 cardiac muscle cell survival pathway is a critical event in the onset of Heart failure during biomechanicalstress. Cell 1999; 97: 189–98.
- Geng, Y, Wu, Q, Muszynski, M, Hansson, GK, Libby, P. Apop-tosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factor alpha, and interleukin-1b. Arterioscler Thromb Vasc Biol 1996; 16: 19–27.
- Li YY Feng YQ Kadokami T et al. Myocardial extracellular matrix remodeling in transgenic mice overexpressing tumor necrosis factor alpha can be modulated by anti-tumor necrosis factor therapy. Proc Natl Acad Sci U S A 2000; 23: 12746–51.
- Sasayama S Okada M Matsumori A. Chemokines and cardiovascular diseases. Cardiovasc Res 2000; 45: 267–9.
- 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.
- Cook DN Beck MA Coffman T. et al. Requirement of MIP-1 alpha for an inflammatory response to viral infection. Science 1995; 269: 1583–5.
- 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.
- Kalra D Sivasubramanian N Mann D.L. Angiotensin II induces tumor necrosis factor biosynthesis in the adult mammalian Heart through a protein kinase C-dependent pathway. Circulation 2002; 105 (18): 2198–205.
- 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.
- Swedberg K Held P Kjekshus J Rasmussen K Ry-den L Wedel H. 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.
- Maisel A.S. Beneficial effects of metoprolol treatment in congestive Heart failure. Reversal of sympathetic-induced alterations of immunological function. Circulation 1994; 90: 1774–80.
- Maisel, AS, Murray D Lotz, M, Rearden A Irwin M, Michel M.C. Propranolol treatment affects parameters of human immunity. Immunopharmacology 1991; 22: 157–64.
- Haraguchi S Good RA Day N.K. Immunosuppressive retroviral peptides: cAMP and cytokine patterns. Immunol Today 1995; 16: 595–603.
- 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 car-diomyopathy. J Am Coll Cardiol 2001; 37: 412–7.
- Gullestad L Ueland T Brunsvig A et al. Effect of meto-prolol on cytokine levels in chronic Heart failure-a sub-study in the Metoprolol Controlled-Release Randomized Intervention Trial in Heart failure (MERIT-HF trial). Am Heart J 2001; 141: 418–21.
- Cleland JG Daubert JC Erdmann E et al. for the Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in Heart failure.[see comment]. N Engl J Med 2005; 352: 1539–49.
- Boriani G Regoli F Saporito D et al. Neurohormones and inflammatory mediators in patients with Heart failure undergoing cardiac resyncronization therapy: time courses and prediction of response. Peptides 2006; 27: 1776–86.
- Bozkurt B Torre-Amione G Warren M. et al. Results of targeted anti-tumor necrosis factor therapy with etaner-cept (ENBREL) in patients with advanced Heart failure. Circulation 2001; 103: 1044–7.
- Gullestad L Aass H Fjeld J. et al. Effect of immunomod-ulating therapy with intravenous immunglobulin in chronic congestive Heart failure. Circulation 2001; 103: 220–5.
- 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.
- Mann DL McMurray JJ Packer M et al. Targeted anti-cytokine therapy in patients with chronic Heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation 2004; 109: 1594–602.
- Lisman KA Stetson SJ Koerner T et al. The role of tumor necrosis factor alpha in the treatment of congestive Heart failure. Congest Heart Fail 2002; 8: 275–9.
- Kadokami T McTiernan CF Kubota T et al. Effects of soluble TNF receptor treatment on lipopolysaccaride-induced myokardial cytokine expression. Am J Physiol 2001; 280: H2281–91.
- Lugering A Schmidt M Lugering N Pauels HG Dom-scke W. Infliximab induces apoptosis in myocytes from patients with chronic active Crohn's Disease by using caspase-dependent pathway. Gastroenterology 2001; 121: 1145–57.
- Evans TJ Moyes D Carpenter A et al. Protective effect of 55- but not 75-kD soluble tumor necrosis factor receptor-immunoglobulin G fusion proteins in an animal model of gram-negative sepsis. J Exp Med 1994; 180 (6): 2173–9.
- Meldrum D.R. Tumor necrosis factor in the Heart. Am J Physiol 1998; 274: R577–95.
- Adamopoulos S Parissis J Karatzas D et al. Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic Heart failure. J Am Coll Cardiol 2002; 39: 653–63.
- Gielen S Adams V Linke A et al. Exercise training in chronic Heart failure: correlation between reduced local inflammation and improved oxidative capacity in the skeletal muscle. Eur J Cardiovasc Prev Rehabil 2005; 12: 393–400.
- Keith M Geranmayegan A Sole M. et al. Increased ox-idative stress in patients with congestive Heart failure. J Am Coll Cardiol 1998; 31: 1352–6.
- Keith, ME, Jeejeebhoy, KN, Langer, A et al. Acontrolledtrial of vitamin E supplementation in patients with congestive Heart failure. Am J Clin Nutr 2001; 73: 219–24.
- Nolan Y Minogue A Vereker E Bolton AE Campbell VA Lynch M.A. Attenuation of LPS-induced changes in synaptic activity in rat hippocampus by Vasogen's immune modulation therapy. Neuroimmunomodulation 2002; 10: 40–6.
- Torre-Amione G Sestier F Radovancevic B Young J. Effects of a novel immune modulation therapy in patients with advanced chronic Heart failure: results of a randomized, controlled, phase II trial. J Am Coll Cardiol 2004; 44: 1181–6.
- Sliwa K Skudicky D Candy G Wisenbaugh T Sareli P. Randomized investigation of effects of pentoxifylline on left ventricular performance in idiopathic dilated car-diomyopathy. Lancet 1998; 351: 1091–3.
- Skudicky D Bergemann A Sliwa K Candy G Sareli P. Beneficial effects of pentoxifylline in patients with idio-pathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol. Circulation 2001; 103: 1083–8.
- Sliwa, K, Woodiwiss, A, Kone, VN et al. Therapyofischemic cardiomyopathy withthe immunomodulatingagent pen-toxifylline: results of a randomized study. Circulation 2004; 109: 750–5.
- Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary artery disease: the Scandinavian Simvas-tatin Survival Study (4S). Lancet 1995; 344: 1383–9.
- The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary Heart disease and a broad range of cholesterol levels. N Engl J Med 1998; 339: 1349–57.
- Kwak B Mulhaup F Mylt S Mach F. Statins as a newly recognized type of immunomodulator. Nat Med 2000; 6: 1399–402.
- Takemoto M Node K Nakagami H et al. Statins as an-tioxidant therapy for preventing cardiac myocyte hypertrophy. J Clin Invest 2001; 108: 1429–37.
- Sola S Mir, MQ, Rajagopalan, S, Helmy T Tandon N Khan B.V. Statin therapy is associated with improved cardiovascular outcomes and levels of inflammatory markers in patients with Heart failure. J Card Fail 2005; 11: 607–12.
- Horwich TB Hamilton MA Maclellan WR Fonarow G.C. Low serum total cholesterol is associated with marked increase in mortality in advanced Heart failure. J Card Fail 2002; 8: 216–24.
- Krum H McMurray J.J. Statins and chronic Heart failure: do we need a large scale outcome trial. J Am Coll Cardiol 2002; 39: 1567–73.
-
Muller J
Wallukat G
Dandel M et al.
Immunoglobulin adsorption in patients with idiopathic dilated cardiomy-opathy.
Circulation
2000;
101:
285–391.
10.1161/01.CIR.101.4.385 Google Scholar
- Staudt A Schaper F Stangl V et al. Immunohistologi-cal changes in dilated cardiomyopathy induced by im-munoadsorption therapy and subsequent immunoglob-ulin substitution. Circulation 2001; 103: 2681–6.
- Ballow M. Mechanism of action of intravenous immune serum globulin in autoimmune and inflammatory diseases. J Allergy Clin Immunol 1997; 100: 151–7.
- Mobini N Sarela A Ahmed A.R. Intravenous im-munoglobulins in the therapy of autoimmune and systemic inflammatory disorders. Ann Allergy Asthma Immunol 1995; 74: 119–28.
- McNamara DM Rosenblum WD Janosko K. et al. Intravenous immune globulin in the therapy of myocarditis and acute cardiomyopathy. Circulation 1997; 95: 2476–8.
- 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.
- McNamara DM Holubkov R Starling R. et al. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation 2001; 103: 2254–9.
- Viard I Wehrli P Schneider P et al. Inhibition of toxic necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science 1998; 282: 490–3.
- Nishio R Matsumori A Shioi T Ishida H Sasayama S. Treatment of experimental viral myocarditis with interleukin-10. Circulation 1999; 100: 1102–8.
- Mallat Z Besnard S Duriez M et al. Protective role of interleukin-10 in atheroscleosis. Cir Res 1999; 85: 17–24.
- Loddick SA Rothwell N.J. Neuroprotective effects of human recombinant interleukin-1 receptor antagonist in focal cerebral ischaemia in the rat. J Cereb Blood Flow Metab 1996; 16: 932–40.
- Ungureanu-Longrois D Balligand J-L Simmons W. et al. Induction of nitric oxide synthase activity by cytokines in ventricular myocytes is necessary but not sufficient to decrease contractile responsivness to pj-adrenergic agonists. Circ Res 1995; 77: 494–502.
- Jacobsen J.M. Thalidomide: a remarkable comeback. Expert Opin Pharmacother 2000; 1: 849–63.
- Adlard J.W. Thalidomide in the treatment of cancer. Anticancer Drugs 2000; 11: 787–91.
- Sampaio EP Sarno EN Galilly R Cohn ZA Kaplan G. Thalidomide selectively inhibits tumor necrosis factor a production by stimulated human monocytes. J Exp Med 1991; 173: 699–703.
- Corral LG Haslett PA Muller G. et al. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol 1999; 163: 380–6.
- Keifer JA Guttridge DC Ashburner AP Baldwin J. Inhibition of NF-kappaB activity by thalidomide through suppression of I kappaB kinase activity. J Biol Chem 2001; 267: 22382–7.
- Zorat F Shetty V Dutt D. The clinical and biological effects of thalidomide in patients with myelodysplastic syndromes. Br J Haematol 2001; 115: 881–94.
- Barlett JB Michael A Clarke I. et al. Phase I study to determine the safety, tolerability and immunostimula-tory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers. Br J Cancer 2004; 90: 955–61.
- Gelati M Corsini E Frigerio S et al. Effects of thalidomide on parameters involved in angiogenesis: an in vitro study. J Neurooncol 2003; 64: 193–201.
- Gullestad L Ueland T Fjeld J et al. The effect of thalido-mide on cardiac remodeling in chronic Heart failure: results of a double-blind placebo-controlled study. Circulation 2005; 112: 3408–14.
- Green J.M. The B7/CD28/CTLA4 T-cell activation pathway. Implications for inflammatory lung disease [review] [53 refs]. Am J Respir Cell Mol Biol 2000; 22 (3): 261–4.
- Salomon B Bluestone J.A. Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation [review] [163 refs]. Ann Rev Immunol 2001; 19: 225–52.
- Lee, MS, Makkar, R.R. Stem-celltransplantation inmyocar-dial infarction:astatus report[seecomment] [review] [80 refs]. Ann Intern Med 2004; 140 (9): 729–37.
- Hayashidani S Tsutsui H Shiomi T et al. Anti-monocyte chemoattractant protein-1 gene therapy attenuates left ventricular remodeling and failure after experimental my-ocardial infarction. Circulation 2003; 108: 2134–40.
-
Suzuki K
Murtuza B
Smolensky R.T.
Overexpression of interleukin-1 receptor antagonist provides cardioprotec-tion against ischemia–reperfusion injury associated with reduction in apoptosis.
Circulation
2001;
104
(suppl I):
I– 308–13.
10.1161/hc37t1.094871 Google Scholar
