Biology of TNFα and IL-10, and their imbalance in heart failure | Springer for Research & Development
This service is more advanced with JavaScript available, learn more at http://activatejavascript.org
Biology of TNFα and IL-10, and their imbalance in heart failureKuljeet KaurSanjiv DhingraJan SlezakAnita K. SharmaAnju BajajPawan K. SingalArticle
Our understanding of the multiple in vivo functions of the proinflammatory cytokine, tumor necrosis factor (TNFα), is advancing at a rapid pace. In addition to its antitumor effects, overproduction of TNFα provokes tissue injury and organ failure. TNFα has also been shown to be cardiodepressent and responsible for various cardiovascular complications. It appears that still much needs to be learned for a full comprehension of the role of TNFα in heart biology. Another cytokine, interleukin-10 (IL-10), has been shown to have anti-inflammatory properties. It is suggested to counterbalance many adverse effects of TNFα. IL-10 suppresses the production of TNFα and many other proinflammatory cytokines. TNFα-induced oxidative stress is also known to be mitigated by IL-10. Moreover, improvement in cardiac function after treatment with various drugs is also shown to be associated with an increase in IL-10 content. Based on the data reviewed in here, it is suggested that an optimal balance between IL-10 and TNFα may be a new therapeutic strategy for a healthier heart.Heart failure Oxidative stress Antioxidants Inflammation This is a preview of subscription content,
to check access.This work was supported by a grant from the Circulatory Respiratory Institute of the CIHR, Canada. Dr. Kuljeet Kaur was supported by the University of Manitoba Graduate Fellowship. Dr. Sanjiv Dhingra is supported by a Postdoctoral Fellowship from the Manitoba Health Research Council and IMPACT Program of CIHR and Heart Foundation. Dr. Pawan Singal is the holder of the Naranjan Dhalla Chair in Cardiovascular Research supported by the St Boniface Hospital & Research Foundation.1.Kaur K, Sharma AK, Singal PK (2006) Significance of changes in TNF-alpha and IL-10 levels in the progression of heart failure subsequent to myocardial infarction. Am J Physiol Heart Circ Physiol 291:H106–H113. doi:
2.Dhingra S, Sharma AK, Singla DK, Singal PK (2007) p38 and ERK 1/2 MAPkinases mediate interplay of TNF-alpha and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis. Am J Physiol Heart Circ Physiol 293:H3524–H3531. doi:
3.Kaur K, Sharma AK, Dhingra S, Singal PK (2006) Interplay of TNF-alpha and IL-10 in regulating oxidative stress in isolated adult cardiac myocytes. J Mol Cell Cardiol 41:. doi:
4.Pulkki KJ (1997) Cytokines and cardiomyocyte death. Ann Med 29:339–343. doi:
5.Yao YY, Yin H, Shen B, Chao L, Chao J (2007) Tissue kallikrein and kinin infusion rescues failing myocardium after myocardial infarction. J Card Fail 13:588–596. doi:
6.Mann DL, Young JB (1994) Basic mechanisms in congestive heart failure. Recognizing the role of proinflammatory cytokines. Chest 105:897–904. doi:
7.Seta Y, Shan K, Bozkurt B, Oral H, Mann DL (1996) Basic mechanisms in heart failure: the cytokine hypothesis. J Card Fail 2:243–249. doi:
8.Langer SE, Scheer JF (1995) Solved—the riddle of illness. Keats Pub, USA9.Deidier A (1725) Dissertation Medecinal et Chirurgical sur les Tumeurs, Paris10.Kolmel K, Pfahlberg A, Mastrangelo G et al (1999) Infections and melanoma risk: results of a multicentre EORTC case-study. Melanoma Res 9:511–51911.Busch W (1868) Aus der Sitzung der medicinischen Section vom 13 November 1867. Berl Klin Wochenschr 5:13712.Bruns P (1888) Die Heilwirkung des Erysipelas auf Geschwülste. Beitr Klin Chir 3:44313.Lassar O (1891) Zur Erysipelimpfung. Dtsch Med Wochenschr 17:88914.Coley WB (1893) The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases. Am J Med Sci 105:487–511. doi:
15.Shear HJ, Marks ES (1962) Measuring self-confining behaviour patterns. J Clin Psychol 18:26–28. doi:10.79(:1&26::AID-JCLP&3.0.CO;2-S16.Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 72:. doi:
17.Aggarwal BB, Henzel WJ, Moffat B, Kohr WJ, Harkins RN (1985) Human tumor necrosis factor: production, purification and characterization. J Biol Chem 260:18.Matthews N (1978) Tumour-necrosis factor from the rabbit. II. Production by monocytes. Br J Cancer 38:310–31519.Fiers W (1991) Tumor necrosis factor. Characterization at the molecular, cellular and in vivo level. FEBS Lett 285:199–221. doi:
20.Spiegelman BM, Hotamisligil GS (1993) Through thick and thin: wasting, obesity, and TNF alpha. Cell 73:625–627. doi:
21.Fiers W, Beyaert R, Brouckaert P et al (1987) Tumor necrosis factor: a potential antitumor agent? J Interferon Res 7:627–63422.Loetscher H, Pan YC, Lahm HW et al (1990) Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell 61:351–359. doi:
23.Smith CA, Davis T, Anderson D et al (1990) A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science 248:. doi:
24.Vandenabeele P, Declercq W, Beyaert R, Fiers W (1995) Two tumour necrosis factor receptors: structure and function. Trends Cell Biol 5:392–399. doi:
25.Grell M, Douni E, Wajant H et al (1995) The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell 83:793–802. doi:
26.Grell M, Wajant H, Zimmermann G, Scheurich P (1998) The type 1 receptor (CD120a) is the high-affinity receptor for soluble tumor necrosis factor. Proc Natl Acad Sci USA 95:570–575. doi:
27.Torre-Amione G, Kapadia S, Lee J, Bies RD, Lebovitz R, Mann DL (1995) Expression and functional significance of tumor necrosis factor receptors in human myocardium. Circulation 92:28.Vassalli P (1992) The pathophysiology of tumor necrosis factors. Annu Rev Immunol 10:411–452. doi:
29.Beutler B, Cerami A (1988) Tumor necrosis, cachexia, shock, and inflammation: a common mediator. Annu Rev Biochem 57:505–518. doi:
30.Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487–501. doi:
31.Loetscher H, Gentz R, Zulauf M et al (1991) Recombinant 55-kDa tumor necrosis factor (TNF) receptor. Stoichiometry of binding to TNF alpha and TNF beta and inhibition of TNF activity. J Biol Chem 266:132.Wajant H, Henkler F, Scheurich P (2001) The TNF-receptor-associated factor family: scaffold molecules for cytokinereceptors, kinases and their regulators. Cell Signal 13:389–400. doi:
33.Tartaglia LA, Ayres TM, Wong GH, Goeddel DV (1993) A novel domain within the 55 kd TNF receptor signals cell death. Cell 74:845–853. doi:
34.Hsu H, Xiong J, Goeddel DV (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81:495–504. doi:
35.Stanger BZ, Leder P, Lee TH, Kim E, Seed B (1995) RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell 81:513–523. doi:
36.Duan H, Dixit VM (1997) RAIDD is a new ‘death’ adaptor molecule. Nature 385:86–89. doi:
37.Enari M, Talanian RV, Wong WW, Nagata S (1996) Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis. Nature 380:723–726. doi:
38.Vanden Berghe W, Plaisance S, Boone E et al (1998) p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways are required for nuclear factor-kappaB p65 transactivation mediated by tumor necrosis factor. J Biol Chem 273:. doi:
39.Chang DJ, Ringold GM, Heller RA (1992) Cell killing and induction of manganous superoxide dismutase by tumor necrosis factor-alpha is mediated by lipoxygenase metabolites of arachidonic acid. Biochem Biophys Res Commun 188:538–546. doi:
40.Kapadia S, Dibbs Z, Kurrelmeyer K et al (1998) The role of cytokines in the failing human heart. Cardiol Clin 16:645–656. doi:
41.Rauchhaus M, Coats AJ, Anker SD (2000) The endotoxin-lipoprotein hypothesis. Lancet 356:930–933. doi:
42.Blick M, Sherwin SA, Rosenblum M, Gutterman J (1987) Phase I study of recombinant tumor necrosis factor in cancer patients. Cancer Res 47:43.Satoh M, Nakamura M, Tamura G et al (1997) Inducible nitric oxide synthase and tumor necrosis factor-alpha in myocardium in human dilated cardiomyopathy. J Am Coll Cardiol 29:716–724. doi:
44.Torre-Amione G, Kapadia S, Lee J et al (1996) Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart. Circulation 93:704–71145.Giroir BP, Johnson JH, Brown T, Allen GL, Beutler B (1992) The tissue distribution of tumor necrosis factor biosynthesis during endotoxemia. J Clin Invest 90:693–698. doi:
46.Kapadia S, Lee J, Torre-Amione G, Birdsall HH, Ma TS, Mann DL (1995) Tumor necrosis factor-alpha gene and protein expression in adult feline myocardium after endotoxin administration. J Clin Invest 96:. doi:
47.Kapadia SR, Oral H, Lee J, Nakano M, Taffet GE, Mann DL (1997) Hemodynamic regulation of tumor necrosis factor-alpha gene and protein expression in adult feline myocardium. Circ Res 81:187–19548.Yue P, Massie BM, Simpson PC, Long CS (1998) Cytokine expression increases in nonmyocytes from rats with postinfarction heart failure. Am J Physiol 275:H250–H25849.Meldrum DR, Cleveland JC Jr, Cain BS, Meng X, Harken AH (1998) Increased myocardial tumor necrosis factor-alpha in a crystalloid-perfusedmodel of cardiac ischemia-reperfusion injury. Ann Thorac Surg 65:439–443. doi:
50.Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, Mann DL (1996) 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 27:. doi:
51.Rauchhaus M, Doehner W, Francis DP et al (2000) Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation 102:52.Ferrari R (1998) Tumor necrosis factor in CHF: a double facet cytokine. Cardiovasc Res 37:554–559. doi:
53.MacGowan GA, Mann DL, Kormos RL, Feldman AM, Murali S (1997) Circulating interleukin-6 in severe heart failure. Am J Cardiol 79:. doi:
54.Testa M, Yeh M, Lee P et al (1996) 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 28:964–971. doi:
55.Torre-Amione G, Stetson SJ, Youker KA et al (1999) Decreased expression of tumor necrosis factor-alpha in failing human myocardium after mechanical circulatory support: a potential mechanism for cardiac recovery. Circulation 100:56.Heard SO, Perkins MW, Fink MP (1992) Tumor necrosis factor-alpha causes myocardial depression in guinea pigs. Crit Care Med 20:523–527. doi:
57.Pagani FD, Baker LS, Hsi C, Knox M, Fink MP, Visner MS (1992) Left ventricular systolic and diastolic dysfunction after infusion of tumor necrosis factor-alpha in conscious dogs. J Clin Invest 90:389–398. doi:
58.Eichenholz PW, Eichacker PQ, Hoffman WD et al (1992) Tumor necrosis factor challenges in canines: patterns of cardiovascular dysfunction. Am J Physiol 263:H668–H67559.Eichacker PQ, Hoffman WD, Farese A et al (1991) TNF but not IL-1 in dogs causes lethal lung injury and multiple organ dysfunction similar to human sepsis. J Appl Physiol 71:60.Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattler BG, Simmons RL (1992) Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 257:387–389. doi:
61.Murray DR, Freeman GL (1996) Tumor necrosis factor-alpha induces a biphasic effect on myocardial contractility in conscious dogs. Circ Res 78:154–16062.Bozkurt B, Kribbs SB, Clubb FJ Jr et al (1998) Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive left ventricular dysfunction and remodeling in rats. Circulation 97:63.Kubota T, McTiernan CF, Frye CS et al (1997) Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ Res 81:627–63564.Nakamura K, Fushimi K, Kouchi H et al (1998) Inhibitory effects of antioxidants on neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor-alpha and angiotensin II. Circulation 98:794–79965.Suematsu N, Tsutsui H, Wen J et al (2003) Oxidative stress mediates tumor necrosis factor-alpha-induced mitochondrial DNA damage and dysfunction in cardiac myocytes. Circulation 107:. doi:
66.Bianchi P, Kunduzova O, Masini E et al (2005) Oxidative stress by monoamine oxidase mediates receptor-independent cardiomyocyte apoptosis by serotonin and postischemic myocardial injury. Circulation 22:. doi:
67.Chaiswing L, Cole MP, St Clair DK, Ittarat W, Szweda LI, Oberley TD (2004) Oxidative damage precedes nitrative damage in adriamycin-induced cardiac mitochondrial injury. Toxicol Pathol 32:536–547. doi:
68.Vlessis AA, Muller P, Bartos D, Trunkey D (1991) Mechanism of peroxide-induced cellular injury in cultured adult cardiac myocytes. FASEB J 5:69.Li YY, Feng YQ, Kadokami T et al (2000) Myocardial extracellular matrix remodeling in transgenic mice overexpressing tumor necrosis factor alpha can be modulated by anti-tumor necrosis factor alpha therapy. Proc Natl Acad Sci USA 97:1. doi:
70.Shen J, O’Brein D, Yi X (2006) Matrix metalloproteinases-2 contributes to tumor necrosis factor alpha induced apoptosis in cultured rat cardiac myocytes. Biochem Biophys Res Commun 347:. doi:
71.Krown KA, Page MT, Nguyen C et al (1996) Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death. J Clin Invest 15:. doi:
72.Cleutjens JP, Kandala JC, Guarda E, Guntaka RV, Weber KT (1995) Regulation of collagen degradation in the rat myocardium after infarction. J Mol Cell Cardiol 27:. doi:
73.Natanson C, Eichenholz PW, Danner RL et al (1989) Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J Exp Med 169:823–832. doi:
74.Castagnoli C, Stella M, Berthod C, Magliacani G, Richiardi PM (1993) TNF production and hypertrophic scarring. Cell Immunol 147:51–563. doi:
75.Rawdanowicz TJ, Hampton AL, Nagase H, Woolley DE, Salamonsen LA (1994) Matrix metalloproteinase production by cultured human endometrial stromal cells: identification of interstitial collagenase, gelatinase-A, gelatinase-B, and stromelysin-1 and their differential regulation by interleukin-1 alpha and tumor necrosis factor-alpha. J Clin Endocrinol Metab 79:530–536. doi:
76.Gottschall PE, Yu X (1995) Cytokines regulate gelatinase A and B (matrix metalloproteinase 2 and 9) activity in cultured rat astrocytes. J Neurochem 64:77.Mann DL, McMurray JJ, Packer M et al (2004) Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation 109:. doi:
78.Bozkurt B, Torre-Amione G, Warren MS et al (2001) Results of targeted anti-tumor necrosis factor therapy with etanercept (ENBREL) in patients with advanced heart failure. Circulation 103:79.Sliwa K, Skudicky D, Candy G, Wisenbaugh T, Sareli P (1998) Randomized investigation of effects of pentoxifylline on left-ventricular performance in idiopathic dilated cardiomyopathy. Lancet 351:. doi:
80.Mohler KM, Sleath PR, Fitzner JN et al (1994) Protection against a lethal dose of endotoxin by an inhibitor of tumour necrosis factor processing. Nature 370:218–220. doi:
81.Moreira AL, Sampaio EP, Zmuidzinas A, Frindt P, Smith KA, Kaplan G (1993) Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med 177:. doi:
82.Parrillo JE, Cunnion RE, Epstein SE et al (1989) A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy. N Engl J Med 321:83.Berthonneche C, Sulpice T, Boucher F et al (2004) New insights into the pathological role of TNF-alpha in early cardiac dysfunction and subsequent heart failure after infarction in rats. Am J Physiol Heart Circ Physiol 287:H340–H350. doi:
84.Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A (1991) IL-10 inhibits cytokine production by activated macrophages. J Immunol (Baltimore, Md.: 15–382285.Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW et al (1991) IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol (Baltimore, Md.: 44–345186.Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765. doi:
87.Wang P, Wu P, Siegel MI, Egan RW, Billah MM (1995) Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. J Biol Chem 270:. doi:
88.Levens JM, Gordon J, Gregory CD (2000) Micro-environmental factors in the survival of human B-lymphoma cells. Cell Death Differ 7:59–69. doi:
89.Moore KW, Vieira P, Fiorentino DF et al (1990) Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science 248:. doi:
90.Howard M, O’Garra A (1992) Biological properties of interleukin 10. Immunol Today 13:198–200. doi:
91.Fickenscher H, Hor S, Kupers H, Knappe A, Wittmann S, Sticht H (2002) The interleukin-10 family of cytokines. Trends Immunol 23:89–96. doi:
92.Platzer C, Volk HD, Platzer M (1994) 5′ noncoding sequence of human IL-10 gene obtained by oligo-cassete PCR walking. DNA Seq 4:399–401. doi:
93.Platzer C, Docke WD, Volk HD, Prosch S (2000) Catecholamines trigger IL-10 release in acute systemic stress reaction by direct stimulation of its promoter/enhancer activity in monocytic cells. J Neuroimmunol 105:31–38. doi:
94.Barsig J, Kusters S, Vogt K, Volk HD, Tiegs G, Wendel A (1995) Lipopolysaccharide-induced IL-10 in mice: role of endogenous TNF-alpha. Eur J Immunol 25:. doi:
95.Meisel C, Vogt K, Platzer C, Randow F, Liebenthal C, Volk HD (1996) Differential regulation of monocytic tumor necrosis factor-alpha and interleukin-10 expression. Eur J Immunol 26:. doi:
96.Ma W, Lim W, Gee K et al (2001) The p38 mitogen-activated kinase pathway regulates the human interleukin-10 promoter via the activation of Sp1 transcription factor in lipopolysaccharide-stimulated human macrophages. J Biol Chem 276:197.Walter MR (2002) Strucure of interleukin-10/interleukin-10R1 complex: a paradigm for class 2 cytokine activation. Immunol Res 26:303–308. doi:
98.Shanley TP, Schmal H, Friedl HP, Jones ML, Ward PA (1995) Regulatory effects of intrinsic IL-10 in IgG immune complex-induced lung injury. J Immunol (Baltimore, Md.: 54–346099.Furukawa Y, Becker G, Stinn JL, Shimizu K, Libby P, Mitchell RN (1999) Interleukin-10 (IL-10) augments allograft arterial disease: paradoxical effects of IL-10 in vivo. Am J Pathol 155:100.vander Poll T, Marchant A, Buurman WA et al (1995) Endogenous IL-10 protects mice from death during septic peritonitis. J Immunol 155:101.Standiford TJ, Strieter RM, Lukacs NW, Kunkel SL (1995) Neutralization of IL-10 increases lethality in endotoxemia. Cooperative effects of macrophage inflammatory protein-2 and tumor necrosis factor. J Immunol (Baltimore, Md.: 22–2229102.Lang R, Rutschman RL, Greaves DR, Murray PJ (2002) Autocrine deactivation of macrophages in transgenic mice constitutively overexpressing IL-10 under control of the human CD68 promoter. J Immunol (Baltimore, Md.: 02–3411103.Hess PJ, Seeger JM, Huber TS et al (1997) Exogenously administered interleukin-10 decreases pulmonary neutrophil infiltration in a tumor necrosis factor-dependent murine model of acute visceral ischemia. J Vasc Surg 26:113–118. doi:
104.Engles RE, Huber TS, Zander DS et al (1997) Exogenous human recombinant interleukin-10 attenuates hindlimb ischemia-reperfusion injury. J Surg Res 69:425–428. doi:
105.Byrne A, Reen DJ (2002) Lipopolysaccharide induces rapid production of IL-10 by monocytes in the presence of apoptotic neutrophils. J Immunol (Baltimore, Md.: 68–1977106.Levy Y, Brouet JC (1994) Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein. J Clin Invest 93:424–428. doi:
107.Finbloom DS, Winestock KD (1995) IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes. J Immunol (Baltimore, Md.: 79–1090108.Clarke CJ, Hales A, Hunt A, Foxwell BM (1998) IL-10-mediated suppression of TNF-alpha production is independent of its ability to inhibit NF kappa B activity. Eur J Immunol 28:. doi:10.1002/(SICI)&1719::AID-IMMU.CO;2-Q109.Schottelius AJ, Mayo MW, Sartor RB, Baldwin AS Jr (1999) Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear factor kappaB DNA binding. J Biol Chem 274:3. doi:
110.Driessler F, Venstrom K, Sabat R, Asadullah K, Schottelius AJ (2004) Molecular mechanisms of interleukin-10-mediated inhibition of NF-kappaB activity: a role for p50. Clin Exp Immunol 135:64–73. doi:
111.Cassatella MA, Gasperini S, Bovolenta C et al (1999) Interleukin-10 (IL-10) selectively enhances CIS3/SOCS3 mRNA expression in human neutrophils: evidence for an IL-10-induced pathway that is independent of STAT protein activation. Blood 94:112.Ito S, Ansari P, Sakatsume M et al (1999) Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma-induced genes by suppressing tyrosine phosphorylation of STAT1. Blood 93:113.Donnelly RP, Dickensheets H, Finbloom DS (1999) The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagocytes. J Interferon Cytokine Res 19:563–573. doi:
114.Berlato C, Cassatella MA, Kinjyo I, Gatto L, Yoshimura A, Bazzoni F (2002) Involvement of suppressor of cytokine signaling-3 as a mediator of the inhibitory effects of IL-10 on lipopolysaccharide-induced macrophage activation. J Immunol (Baltimore, Md.: 04–6411115.Lee TS, Chau LY (2002) Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 8:240–246. doi:
116.Pezzilli R, Billi P, Miniero R, Dig BB (1997) Serum interleukin-10 in human acute pancreatitis. Dis Sci 42:. doi:
117.Bogdan C, Vodovotz Y, Nathan C (1991) Macrophage deactivation by interleukin 10. J Exp Med 174:. doi:
118.Kwon OJ (1997) The role of nitric oxide in the immune response of tuberculosis Korean. Med Sci 12:481–487119.Gougerot-Podicalo MA, Elbim C, Chollet-Martin S
(1996) Modulation by pro- and anti-inflammatory cytokines of the oxidative burst of human neutrophils. Pathol Biol (Paris) 44:36–41120.Dandona P, Mohanty P, Hamouda W, Aljada A, Kumbkarni Y, Garg R (1999) Effect of dexamethasone on reactive oxygen species generation by leukocytes and plasma interleukin-10 concentrations: a pharmacodynamic study. Clin Pharmacol Ther 66:58–65. doi:
121.Mulligan MS, Jones ML, Vaporciyan AA, Howard MC, Ward PA (1993) Protective effects of IL-4 and IL-10 against immune complex-induced lung injury. J Immunol (Baltimore, Md.: 66–5674122.Shanley TP, Schmal H, Friedl HP, Jones ML, Ward PA (1995) Role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in acute lung injury in rats. J Immunol (Baltimore, Md.: 93–4802123.Gunnett CA, Heistad DD, Berg DJ, Faraci FM (2000) IL-10 deficiency increases superoxide and endothelial dysfunction during inflammation. Am J Physiol Heart Circ Physiol 279:H1555–H1562124.Keel M, Ungethum U, Steckholzer E et al (1997) Interleukin-10 counterregulates proinflammatory cytokine-induced inhibition of neutrophil apoptosis during severe sepsis. Blood 90:125.Adamopoulos S, Parissis JT, Paraskevaidis I et al (2003) Effects of growth hormone on circulating cytokine network, and left ventricular contractile performance and geometry in patients with idiopathic dilated cardiomyopathy. Eur Heart J 24:. doi:
126.El Azab SR, Rosseel PM, de Lange JJ et al (2002) Dexamethasone decreases the pro- to anti inflammatory cytokine ratio during cardiac surgery. Br J Anaesth 88:496–501. doi:
127.Giomarelli P, Scolletta S, Borrelli E, Biagioli B (2003) Myocardial and lung injury after cardiopulmonary bypass: role of interleukin (IL)-10. Ann Thorac Surg 76:117–123. doi:
128.Lacraz S, Nicod LP, Chicheportiche R, Welgus HG, Dayer JM (1995) IL-10 inhibits metalloproteinase and stimulates TIMP-1 production in human mononuclear phagocytes. J Clin Invest 96:. doi:
129.Ksontini R, MacKay SL, Moldawer LL (1998) Revisiting the role of tumor necrosis factor alpha and the response to surgical injury and inflammation. Arch Surg 133:558–567. doi:
130.Cassatella MA, Meda L, Gasperini S, Calzetti F, Bonora S (1994) Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation. J Exp Med 179:. doi:
131.Kasama T, Strieter RM, Lukacs NW, Lincoln PM, Burdick MD, Kunkel SL (1995) Interleukin-10 expression and chemokine regulation during the evolution of murine type II collagen-induced arthritis. J Clin Invest 95:. doi:
132.Wang P, Wu P, Anthes JC, Siegel MI, Egan RW, Billah MM (1994) Interleukin-10 inhibits interleukin-8 production in human neutrophils. Blood 83:133.Howard M, Muchamuel T, Andrade S, Menon S (1993) Interleukin 10 protects mice from lethal endotoxemia. J Exp Med 177:. doi:
134.Gerard C, Bruyns C, Marchant A et al (1993) Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. J Exp Med 177:547–550. doi:
135.Fearon DT, Locksley RM (1996) The instructive role of innate immunity in the acquired immune response. Science 272:50–53. doi:
136.Mosmann TR, Sad S (1996) The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 17:138–146. doi:
137.Stumpf C, Lehner C, Yilmaz A, Daniel WG, Garlichs CD (2003) Decrease of serum levels of the anti-inflammatory cytokine interleukin-10 in patients with advanced chronic heart failure. Clin Sci 105:45–50. doi:
138.Waehre T, Halvorsen B, Damas JK et al (2002) Inflammatory imbalance between IL-10 and TNFalpha in unstable angina potential plaque stabilizing effects of IL-10. Eur J Clin Invest 32:803–810. doi:
139.Lentsch AB, Shanley TP, Sarma V, Ward PA (1997) In vivo suppression of NF-kappa B and preservation of I kappa B alpha by interleukin-10 and interleukin-13. J Clin Invest 15:. doi:
140.Shan K, Kurrelmeyer K, Seta Y et al (1997) The role of cytokines in disease progression in heart failure. Curr Opin Cardiol 12:218–223. doi:
141.Meldrum DR (1998) Tumor necrosis factor in the heart. Am J Physiol 274:R577–R595142.Mann DL (1996) The effect of tumor necrosis factor-alpha on cardiac structure and function: a tale of two cytokines. J Card Fail 2:S165–S172. doi:
143.Kelly A, Lynch E, Vereker Y et al (2001) The anti-inflammatory cytokine, interleukin (IL)-10, blocks the inhibitory effect of IL-1 beta on long term potentiation. A role for JNK. J Biol Chem 276:4. doi:
Kuljeet Kaur1Sanjiv Dhingra23Jan Slezak4Anita K. Sharma23Anju Bajaj23Pawan K. Singal231.Department of PharmacologyThe University of MichiganAnn ArborUSA2.Institute of Cardiovascular SciencesSt. Boniface General Hospital Research CenterWinnipegCanada3.Department of Physiology, Faculty of MedicineUniversity of ManitobaWinnipegCanada4.Institute for Heart ResearchSlovak Academy of SciencesBratislavaSlovak Republic