Skip to main content
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1997 Jun;6(3):175–183. doi: 10.1080/09629359791668

Role of cytokines in myocardial ischemia and reperfusion

H S Sharma 1,, D K Das 2
PMCID: PMC2365828  PMID: 18472818

Abstract

Mediators of myocardial inflammation, predominantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the inflammation may result in deleterious complications for myocardial infarction. The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of literature suggests that inflammatory mediators could play a crucial role in ischemia–reperfusion injury. Furthermore, ischemia–reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypoxia causes a series of well documented changes in cardiomyocytes that includes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypoxic cardiomyocytes produce interleukin-6 (IL-6) which could contribute to the myocardial dysfunction observed in ischemia reperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF), in the heart. Intrestingly, these multipotent cytokines (e.g. TNF-α) may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have included a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart.

Full Text

The Full Text of this article is available as a PDF (218.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akira S., Hirano T., Taga T., Kishimoto T. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J. 1990 Aug;4(11):2860–2867. [PubMed] [Google Scholar]
  2. Andres J., Sharma H. S., Knöll R., Stahl J., Sassen L. M., Verdouw P. D., Schaper W. Expression of heat shock proteins in the normal and stunned porcine myocardium. Cardiovasc Res. 1993 Aug;27(8):1421–1429. doi: 10.1093/cvr/27.8.1421. [DOI] [PubMed] [Google Scholar]
  3. Bagchi D., Das D. K., Engelman R. M., Prasad M. R., Subramanian R. Polymorphonuclear leucocytes as potential source of free radicals in the ischaemic-reperfused myocardium. Eur Heart J. 1990 Sep;11(9):800–813. doi: 10.1093/oxfordjournals.eurheartj.a059800. [DOI] [PubMed] [Google Scholar]
  4. Balligand J. L., Ungureanu-Longrois D., Simmons W. W., Pimental D., Malinski T. A., Kapturczak M., Taha Z., Lowenstein C. J., Davidoff A. J., Kelly R. A. Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes. Characterization and regulation of iNOS expression and detection of iNOS activity in single cardiac myocytes in vitro. J Biol Chem. 1994 Nov 4;269(44):27580–27588. [PubMed] [Google Scholar]
  5. Bendtzen K. Interleukin 1, interleukin 6 and tumor necrosis factor in infection, inflammation and immunity. Immunol Lett. 1988 Nov;19(3):183–191. doi: 10.1016/0165-2478(88)90141-1. [DOI] [PubMed] [Google Scholar]
  6. Bolli R. Mechanism of myocardial "stunning". Circulation. 1990 Sep;82(3):723–738. doi: 10.1161/01.cir.82.3.723. [DOI] [PubMed] [Google Scholar]
  7. Brand T., Sharma H. S., Fleischmann K. E., Duncker D. J., McFalls E. O., Verdouw P. D., Schaper W. Proto-oncogene expression in porcine myocardium subjected to ischemia and reperfusion. Circ Res. 1992 Dec;71(6):1351–1360. doi: 10.1161/01.res.71.6.1351. [DOI] [PubMed] [Google Scholar]
  8. Chenoweth D. E., Cooper S. W., Hugli T. E., Stewart R. W., Blackstone E. H., Kirklin J. W. Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med. 1981 Feb 26;304(9):497–503. doi: 10.1056/NEJM198102263040901. [DOI] [PubMed] [Google Scholar]
  9. Ciocca D. R., Oesterreich S., Chamness G. C., McGuire W. L., Fuqua S. A. Biological and clinical implications of heat shock protein 27,000 (Hsp27): a review. J Natl Cancer Inst. 1993 Oct 6;85(19):1558–1570. doi: 10.1093/jnci/85.19.1558. [DOI] [PubMed] [Google Scholar]
  10. Das D. K., Engelman R. M., Kimura Y. Molecular adaptation of cellular defences following preconditioning of the heart by repeated ischaemia. Cardiovasc Res. 1993 Apr;27(4):578–584. doi: 10.1093/cvr/27.4.578. [DOI] [PubMed] [Google Scholar]
  11. Das D. K., Engelman R. M., Rousou J. A., Breyer R. H., Otani H., Lemeshow S. Pathophysiology of superoxide radical as potential mediator of reperfusion injury in pig heart. Basic Res Cardiol. 1986 Mar-Apr;81(2):155–166. doi: 10.1007/BF01907380. [DOI] [PubMed] [Google Scholar]
  12. Dinarello C. A. Biology of interleukin 1. FASEB J. 1988 Feb;2(2):108–115. [PubMed] [Google Scholar]
  13. Eddy L. J., Goeddel D. V., Wong G. H. Tumor necrosis factor-alpha pretreatment is protective in a rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun. 1992 Apr 30;184(2):1056–1059. doi: 10.1016/0006-291x(92)90698-k. [DOI] [PubMed] [Google Scholar]
  14. Eghbali M. Cellular origin and distribution of transforming growth factor-beta in the normal rat myocardium. Cell Tissue Res. 1989 Jun;256(3):553–558. doi: 10.1007/BF00225603. [DOI] [PubMed] [Google Scholar]
  15. Engel K., Ahlers A., Brach M. A., Herrmann F., Gaestel M. MAPKAP kinase 2 is activated by heat shock and TNF-alpha: in vivo phosphorylation of small heat shock protein results from stimulation of the MAP kinase cascade. J Cell Biochem. 1995 Feb;57(2):321–330. doi: 10.1002/jcb.240570216. [DOI] [PubMed] [Google Scholar]
  16. Engelman D. T., Watanabe M., Engelman R. M., Rousou J. A., Flack J. E., 3rd, Deaton D. W., Das D. K. Constitutive nitric oxide release is impaired after ischemia and reperfusion. J Thorac Cardiovasc Surg. 1995 Oct;110(4 Pt 1):1047–1053. doi: 10.1016/s0022-5223(05)80173-4. [DOI] [PubMed] [Google Scholar]
  17. Evans H. G., Lewis M. J., Shah A. M. Interleukin-1 beta modulates myocardial contraction via dexamethasone sensitive production of nitric oxide. Cardiovasc Res. 1993 Aug;27(8):1486–1490. doi: 10.1093/cvr/27.8.1486. [DOI] [PubMed] [Google Scholar]
  18. Finkel M. S., Hoffman R. A., Shen L., Oddis C. V., Simmons R. L., Hattler B. G. Interleukin-6 (IL-6) as a mediator of stunned myocardium. Am J Cardiol. 1993 May 15;71(13):1231–1232. doi: 10.1016/0002-9149(93)90654-u. [DOI] [PubMed] [Google Scholar]
  19. Folkman J., Shing Y. Angiogenesis. J Biol Chem. 1992 Jun 5;267(16):10931–10934. [PubMed] [Google Scholar]
  20. Fosse E., Mollnes T. E., Ingvaldsen B. Complement activation during major operations with or without cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1987 Jun;93(6):860–866. [PubMed] [Google Scholar]
  21. Frass O., Sharma H. S., Knöll R., Duncker D. J., McFalls E. O., Verdouw P. D., Schaper W. Enhanced gene expression of calcium regulatory proteins in stunned porcine myocardium. Cardiovasc Res. 1993 Nov;27(11):2037–2043. doi: 10.1093/cvr/27.11.2037. [DOI] [PubMed] [Google Scholar]
  22. Geiger T., Andus T., Klapproth J., Hirano T., Kishimoto T., Heinrich P. C. Induction of rat acute-phase proteins by interleukin 6 in vivo. Eur J Immunol. 1988 May;18(5):717–721. doi: 10.1002/eji.1830180510. [DOI] [PubMed] [Google Scholar]
  23. Görge G., Schmidt T., Ito B. R., Pantely G. A., Schaper W. Microvascular and collateral adaptation in swine hearts following progressive coronary artery stenosis. Basic Res Cardiol. 1989 Sep-Oct;84(5):524–535. doi: 10.1007/BF01908204. [DOI] [PubMed] [Google Scholar]
  24. Haeffner-Cavaillon N., Roussellier N., Ponzio O., Carreno M. P., Laude M., Carpentier A., Kazatchkine M. D. Induction of interleukin-1 production in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1989 Dec;98(6):1100–1106. [PubMed] [Google Scholar]
  25. Han R. O., Ray P. E., Baughman K. L., Feldman A. M. Detection of interleukin and interleukin-receptor mRNA in human heart by polymerase chain reaction. Biochem Biophys Res Commun. 1991 Dec 16;181(2):520–523. doi: 10.1016/0006-291x(91)91219-3. [DOI] [PubMed] [Google Scholar]
  26. Hayashi T., Takada K., Matsuda M. Post-transient ischemia increase in ubiquitin conjugates in the early reperfusion. Neuroreport. 1992 Jun;3(6):519–520. doi: 10.1097/00001756-199206000-00016. [DOI] [PubMed] [Google Scholar]
  27. Heads R. J., Yellon D. M., Latchman D. S. Differential cytoprotection against heat stress or hypoxia following expression of specific stress protein genes in myogenic cells. J Mol Cell Cardiol. 1995 Aug;27(8):1669–1678. doi: 10.1016/s0022-2828(95)90722-x. [DOI] [PubMed] [Google Scholar]
  28. Hennein H. A., Ebba H., Rodriguez J. L., Merrick S. H., Keith F. M., Bronstein M. H., Leung J. M., Mangano D. T., Greenfield L. J., Rankin J. S. Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. J Thorac Cardiovasc Surg. 1994 Oct;108(4):626–635. [PubMed] [Google Scholar]
  29. Hershko A., Ciechanover A. The ubiquitin system for protein degradation. Annu Rev Biochem. 1992;61:761–807. doi: 10.1146/annurev.bi.61.070192.003553. [DOI] [PubMed] [Google Scholar]
  30. Herskowitz A., Choi S., Ansari A. A., Wesselingh S. Cytokine mRNA expression in postischemic/reperfused myocardium. Am J Pathol. 1995 Feb;146(2):419–428. [PMC free article] [PubMed] [Google Scholar]
  31. Hind C. R., Griffin J. F., Pack S., Latchman Y. E., Drake H. F., Jones H. M., Brostoff J., Dormandy T. L., Treasures T. Effect of cardiopulmonary bypass on circulating concentrations of leucocyte elastase and free radical activity. Cardiovasc Res. 1988 Jan;22(1):37–41. doi: 10.1093/cvr/22.1.37. [DOI] [PubMed] [Google Scholar]
  32. Ikeda U., Ikeda M., Kano S., Shimada K. Neutrophil adherence to rat cardiac myocyte by proinflammatory cytokines. J Cardiovasc Pharmacol. 1994 Apr;23(4):647–652. doi: 10.1097/00005344-199404000-00019. [DOI] [PubMed] [Google Scholar]
  33. Ikeda U., Ohkawa F., Seino Y., Yamamoto K., Hidaka Y., Kasahara T., Kawai T., Shimada K. Serum interleukin 6 levels become elevated in acute myocardial infarction. J Mol Cell Cardiol. 1992 Jun;24(6):579–584. doi: 10.1016/0022-2828(92)91042-4. [DOI] [PubMed] [Google Scholar]
  34. JENNINGS R. B., SOMMERS H. M., SMYTH G. A., FLACK H. A., LINN H. Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Arch Pathol. 1960 Jul;70:68–78. [PubMed] [Google Scholar]
  35. Jennings R. B., Schaper J., Hill M. L., Steenbergen C., Jr, Reimer K. A. Effect of reperfusion late in the phase of reversible ischemic injury. Changes in cell volume, electrolytes, metabolites, and ultrastructure. Circ Res. 1985 Feb;56(2):262–278. doi: 10.1161/01.res.56.2.262. [DOI] [PubMed] [Google Scholar]
  36. Jentsch S. Ubiquitin-dependent protein degradation: a cellular perspective. Trends Cell Biol. 1992 Apr;2(4):98–103. doi: 10.1016/0962-8924(92)90013-d. [DOI] [PubMed] [Google Scholar]
  37. Johnson P. F., McKnight S. L. Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem. 1989;58:799–839. doi: 10.1146/annurev.bi.58.070189.004055. [DOI] [PubMed] [Google Scholar]
  38. Kaur P., Welch W. J., Saklatvala J. Interleukin 1 and tumour necrosis factor increase phosphorylation of the small heat shock protein. Effects in fibroblasts, Hep G2 and U937 cells. FEBS Lett. 1989 Dec 4;258(2):269–273. doi: 10.1016/0014-5793(89)81671-0. [DOI] [PubMed] [Google Scholar]
  39. Kilian P. L., Kaffka K. L., Stern A. S., Woehle D., Benjamin W. R., Dechiara T. M., Gubler U., Farrar J. J., Mizel S. B., Lomedico P. T. Interleukin 1 alpha and interleukin 1 beta bind to the same receptor on T cells. J Immunol. 1986 Jun 15;136(12):4509–4514. [PubMed] [Google Scholar]
  40. Knowlton A. A., Brecher P., Apstein C. S. Rapid expression of heat shock protein in the rabbit after brief cardiac ischemia. J Clin Invest. 1991 Jan;87(1):139–147. doi: 10.1172/JCI114963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Knowlton A. A. The role of heat shock proteins in the heart. J Mol Cell Cardiol. 1995 Jan;27(1):121–131. doi: 10.1016/s0022-2828(08)80012-0. [DOI] [PubMed] [Google Scholar]
  42. Kukielka G. L., Youker K. A., Hawkins H. K., Perrard J. L., Michael L. H., Ballantyne C. M., Smith C. W., Entman M. L. Regulation of ICAM-1 and IL-6 in myocardial ischemia: effect of reperfusion. Ann N Y Acad Sci. 1994 Jun 17;723:258–270. [PubMed] [Google Scholar]
  43. Kusuoka H., Marban E. Cellular mechanisms of myocardial stunning. Annu Rev Physiol. 1992;54:243–256. doi: 10.1146/annurev.ph.54.030192.001331. [DOI] [PubMed] [Google Scholar]
  44. Lefer A. M. Mechanisms of the protective effects of transforming growth factor-beta in reperfusion injury. Biochem Pharmacol. 1991 Sep 12;42(7):1323–1327. doi: 10.1016/0006-2952(91)90441-7. [DOI] [PubMed] [Google Scholar]
  45. Lefer A. M., Tsao P., Aoki N., Palladino M. A., Jr Mediation of cardioprotection by transforming growth factor-beta. Science. 1990 Jul 6;249(4964):61–64. doi: 10.1126/science.2164258. [DOI] [PubMed] [Google Scholar]
  46. Loppnow H., Libby P. Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6. J Clin Invest. 1990 Mar;85(3):731–738. doi: 10.1172/JCI114498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Lord P. C., Wilmoth L. M., Mizel S. B., McCall C. E. Expression of interleukin-1 alpha and beta genes by human blood polymorphonuclear leukocytes. J Clin Invest. 1991 Apr;87(4):1312–1321. doi: 10.1172/JCI115134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Lucchesi B. R., Mullane K. M. Leukocytes and ischemia-induced myocardial injury. Annu Rev Pharmacol Toxicol. 1986;26:201–224. doi: 10.1146/annurev.pa.26.040186.001221. [DOI] [PubMed] [Google Scholar]
  49. Löw-Friedrich I., Weisensee D., Mitrou P., Schoeppe W. Cytokines induce stress protein formation in cultured cardiac myocytes. Basic Res Cardiol. 1992 Jan-Feb;87(1):12–18. doi: 10.1007/BF00795385. [DOI] [PubMed] [Google Scholar]
  50. MacLellan W. R., Brand T., Schneider M. D. Transforming growth factor-beta in cardiac ontogeny and adaptation. Circ Res. 1993 Nov;73(5):783–791. doi: 10.1161/01.res.73.5.783. [DOI] [PubMed] [Google Scholar]
  51. Maulik N., Sharma H. S., Das D. K. Induction of the haem oxygenase gene expression during the reperfusion of ischemic rat myocardium. J Mol Cell Cardiol. 1996 Jun;28(6):1261–1270. doi: 10.1006/jmcc.1996.0116. [DOI] [PubMed] [Google Scholar]
  52. Maulik N., Watanabe M., Engelman D. T., Engelman R. M., Das D. K. Oxidative stress adaptation improves postischemic ventricular recovery. Mol Cell Biochem. 1995 Mar 9;144(1):67–74. doi: 10.1007/BF00926742. [DOI] [PubMed] [Google Scholar]
  53. Mehlen P., Mehlen A., Guillet D., Preville X., Arrigo A. P. Tumor necrosis factor-alpha induces changes in the phosphorylation, cellular localization, and oligomerization of human hsp27, a stress protein that confers cellular resistance to this cytokine. J Cell Biochem. 1995 Jun;58(2):248–259. doi: 10.1002/jcb.240580213. [DOI] [PubMed] [Google Scholar]
  54. Mestril R., Dillmann W. H. Heat shock proteins and protection against myocardial ischemia. J Mol Cell Cardiol. 1995 Jan;27(1):45–52. doi: 10.1016/s0022-2828(08)80006-5. [DOI] [PubMed] [Google Scholar]
  55. Morimoto S., Nabata T., Koh E., Shiraishi T., Fukuo K., Imanaka S., Kitano S., Miyashita Y., Ogihara T. Interleukin-6 stimulates proliferation of cultured vascular smooth muscle cells independently of interleukin-1 beta. J Cardiovasc Pharmacol. 1991;17 (Suppl 2):S117–S118. doi: 10.1097/00005344-199117002-00026. [DOI] [PubMed] [Google Scholar]
  56. Murry C. E., Richard V. J., Reimer K. A., Jennings R. B. Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode. Circ Res. 1990 Apr;66(4):913–931. doi: 10.1161/01.res.66.4.913. [DOI] [PubMed] [Google Scholar]
  57. Mustoe T. A., Pierce G. F., Thomason A., Gramates P., Sporn M. B., Deuel T. F. Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science. 1987 Sep 11;237(4820):1333–1336. doi: 10.1126/science.2442813. [DOI] [PubMed] [Google Scholar]
  58. Nilsson L., Brunnkvist S., Nilsson U., Nyström S. O., Tydén H., Venge P., Aberg T. Activation of inflammatory systems during cardiopulmonary bypass. Scand J Thorac Cardiovasc Surg. 1988;22(1):51–53. doi: 10.3109/14017438809106051. [DOI] [PubMed] [Google Scholar]
  59. Nogae C., Makino N., Hata T., Nogae I., Takahashi S., Suzuki K., Taniguchi N., Yanaga T. Interleukin 1 alpha-induced expression of manganous superoxide dismutase reduces myocardial reperfusion injury in the rat. J Mol Cell Cardiol. 1995 Oct;27(10):2091–2099. doi: 10.1016/s0022-2828(95)91155-3. [DOI] [PubMed] [Google Scholar]
  60. Okusawa S., Gelfand J. A., Ikejima T., Connolly R. J., Dinarello C. A. Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition. J Clin Invest. 1988 Apr;81(4):1162–1172. doi: 10.1172/JCI113431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Otani H., Engelman R. M., Rousou J. A., Breyer R. H., Das D. K. Enhanced prostaglandin synthesis due to phospholipid breakdown in ischemic-reperfused myocardium. Control of its production by a phospholipase inhibitor or free radical scavengers. J Mol Cell Cardiol. 1986 Sep;18(9):953–961. doi: 10.1016/s0022-2828(86)80009-8. [DOI] [PubMed] [Google Scholar]
  62. Reithmann C., Gierschik P., Werdan K., Jakobs K. H. Tumor necrosis factor alpha up-regulates Gi alpha and G beta proteins and adenylyl cyclase responsiveness in rat cardiomyocytes. Eur J Pharmacol. 1991 Jan 25;206(1):53–60. doi: 10.1016/0922-4106(91)90146-9. [DOI] [PubMed] [Google Scholar]
  63. Roberts A. B., Sporn M. B., Assoian R. K., Smith J. M., Roche N. S., Wakefield L. M., Heine U. I., Liotta L. A., Falanga V., Kehrl J. H. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167–4171. doi: 10.1073/pnas.83.12.4167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Rothe J., Gehr G., Loetscher H., Lesslauer W. Tumor necrosis factor receptors--structure and function. Immunol Res. 1992;11(2):81–90. doi: 10.1007/BF02918612. [DOI] [PubMed] [Google Scholar]
  65. Rozanski G. J., Witt R. C. IL-1 inhibits beta-adrenergic control of cardiac calcium current: role of L-arginine/nitric oxide pathway. Am J Physiol. 1994 Nov;267(5 Pt 2):H1753–H1758. doi: 10.1152/ajpheart.1994.267.5.H1753. [DOI] [PubMed] [Google Scholar]
  66. Rubartelli A., Cozzolino F., Talio M., Sitia R. A novel secretory pathway for interleukin-1 beta, a protein lacking a signal sequence. EMBO J. 1990 May;9(5):1503–1510. doi: 10.1002/j.1460-2075.1990.tb08268.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Schaper W., Schaper J. Adaptation to and defense against myocardial ischemia. Cardiology. 1990;77(5):367–372. doi: 10.1159/000174626. [DOI] [PubMed] [Google Scholar]
  68. Schott R. J., Rohmann S., Braun E. R., Schaper W. Ischemic preconditioning reduces infarct size in swine myocardium. Circ Res. 1990 Apr;66(4):1133–1142. doi: 10.1161/01.res.66.4.1133. [DOI] [PubMed] [Google Scholar]
  69. Schulz R., Nava E., Moncada S. Induction and potential biological relevance of a Ca(2+)-independent nitric oxide synthase in the myocardium. Br J Pharmacol. 1992 Mar;105(3):575–580. doi: 10.1111/j.1476-5381.1992.tb09021.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Sharma H. S., Maulik N., Gho B. C., Das D. K., Verdouw P. D. Coordinated expression of heme oxygenase-1 and ubiquitin in the porcine heart subjected to ischemia and reperfusion. Mol Cell Biochem. 1996 Apr 12;157(1-2):111–116. doi: 10.1007/BF00227888. [DOI] [PubMed] [Google Scholar]
  71. Sharma H. S., Snoeckx L. H., Sassen L. M., Knöll R., Andres J., Verdouw P. D., Schaper W. Expression and immunohistochemical localization of heat-shock protein-70 in preconditioned porcine myocardium. Ann N Y Acad Sci. 1994 Jun 17;723:491–494. [PubMed] [Google Scholar]
  72. Sharma H. S., Stahl J., Weisensee D., Löw-Friedrich I. Cytoprotective mechanisms in cultured cardiomyocytes. Mol Cell Biochem. 1996 Jul-Aug;160-161:217–224. doi: 10.1007/BF00240052. [DOI] [PubMed] [Google Scholar]
  73. Sharma H. S., Verdouw P. D., Lamers J. M. Involvement of the sarcoplasmic reticulum calcium pump in myocardial contractile dysfunction: comparison between chronic pressure-overload and stunning. Cardiovasc Drugs Ther. 1994 Jun;8(3):461–468. doi: 10.1007/BF00877923. [DOI] [PubMed] [Google Scholar]
  74. Sharma H. S., Weisensee D., Löw-Friedrich I. Tumor necrosis factor-alpha-induced cytoprotective mechanisms in cardiomyocytes. Analysis by mRNA phenotyping. Ann N Y Acad Sci. 1996 Sep 30;793:267–281. doi: 10.1111/j.1749-6632.1996.tb33520.x. [DOI] [PubMed] [Google Scholar]
  75. Sharma H. S., Wünsch M., Brand T., Verdouw P. D., Schaper W. Molecular biology of the coronary vascular and myocardial responses to ischemia. J Cardiovasc Pharmacol. 1992;20 (Suppl 1):S23–S31. [PubMed] [Google Scholar]
  76. Sherry B., Cerami A. Cachectin/tumor necrosis factor exerts endocrine, paracrine, and autocrine control of inflammatory responses. J Cell Biol. 1988 Oct;107(4):1269–1277. doi: 10.1083/jcb.107.4.1269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Spriggs D. R., Sherman M. L., Imamura K., Mohri M., Rodriguez C., Robbins G., Kufe D. W. Phospholipase A2 activation and autoinduction of tumor necrosis factor gene expression by tumor necrosis factor. Cancer Res. 1990 Nov 15;50(22):7101–7107. [PubMed] [Google Scholar]
  78. Tartaglia L. A., Weber R. F., Figari I. S., Reynolds C., Palladino M. A., Jr, Goeddel D. V. The two different receptors for tumor necrosis factor mediate distinct cellular responses. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9292–9296. doi: 10.1073/pnas.88.20.9292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Thelen M., Peveri P., Kernen P., von Tscharner V., Walz A., Baggiolini M. Mechanism of neutrophil activation by NAF, a novel monocyte-derived peptide agonist. FASEB J. 1988 Aug;2(11):2702–2706. [PubMed] [Google Scholar]
  80. Torre-Amione G., Kapadia S., Lee J., Durand J. B., Bies R. D., Young J. B., Mann D. L. Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart. Circulation. 1996 Feb 15;93(4):704–711. doi: 10.1161/01.cir.93.4.704. [DOI] [PubMed] [Google Scholar]
  81. Tracey K. J., Cerami A. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu Rev Med. 1994;45:491–503. doi: 10.1146/annurev.med.45.1.491. [DOI] [PubMed] [Google Scholar]
  82. Tsujino M., Hirata Y., Imai T., Kanno K., Eguchi S., Ito H., Marumo F. Induction of nitric oxide synthase gene by interleukin-1 beta in cultured rat cardiocytes. Circulation. 1994 Jul;90(1):375–383. doi: 10.1161/01.cir.90.1.375. [DOI] [PubMed] [Google Scholar]
  83. Vaddi K., Nicolini F. A., Mehta P., Mehta J. L. Increased secretion of tumor necrosis factor-alpha and interferon-gamma by mononuclear leukocytes in patients with ischemic heart disease. Relevance in superoxide anion generation. Circulation. 1994 Aug;90(2):694–699. doi: 10.1161/01.cir.90.2.694. [DOI] [PubMed] [Google Scholar]
  84. Walsh C. J., Sugerman H. J., Mullen P. G., Carey P. D., Leeper-Woodford S. K., Jesmok G. J., Ellis E. F., Fowler A. A. Monoclonal antibody to tumor necrosis factor alpha attenuates cardiopulmonary dysfunction in porcine gram-negative sepsis. Arch Surg. 1992 Feb;127(2):138–145. doi: 10.1001/archsurg.1992.01420020020003. [DOI] [PubMed] [Google Scholar]
  85. Weisensee D., Bereiter-Hahn J., Schoeppe W., Löw-Friedrich I. Effects of cytokines on the contractility of cultured cardiac myocytes. Int J Immunopharmacol. 1993 Jul;15(5):581–587. doi: 10.1016/0192-0561(93)90075-a. [DOI] [PubMed] [Google Scholar]
  86. Welch W. J. Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol Rev. 1992 Oct;72(4):1063–1081. doi: 10.1152/physrev.1992.72.4.1063. [DOI] [PubMed] [Google Scholar]
  87. Whicher J. T., Evans S. W. Cytokines in disease. Clin Chem. 1990 Jul;36(7):1269–1281. [PubMed] [Google Scholar]
  88. Wiegmann K., Schütze S., Kampen E., Himmler A., Machleidt T., Krönke M. Human 55-kDa receptor for tumor necrosis factor coupled to signal transduction cascades. J Biol Chem. 1992 Sep 5;267(25):17997–18001. [PubMed] [Google Scholar]
  89. Wünsch M., Sharma H. S., Markert T., Bernotat-Danielowski S., Schott R. J., Kremer P., Bleese N., Schaper W. In situ localization of transforming growth factor beta 1 in porcine heart: enhanced expression after chronic coronary artery constriction. J Mol Cell Cardiol. 1991 Sep;23(9):1051–1062. doi: 10.1016/0022-2828(91)91640-d. [DOI] [PubMed] [Google Scholar]
  90. Yamada M., Sohmura Y., Nakamura S., Hashimoto M. Interleukin-1 alpha: its possible roles in cancer therapy. Biotherapy. 1989;1(4):327–338. doi: 10.1007/BF02171009. [DOI] [PubMed] [Google Scholar]
  91. Yamauchi-Takihara K., Ihara Y., Ogata A., Yoshizaki K., Azuma J., Kishimoto T. Hypoxic stress induces cardiac myocyte-derived interleukin-6. Circulation. 1995 Mar 1;91(5):1520–1524. doi: 10.1161/01.cir.91.5.1520. [DOI] [PubMed] [Google Scholar]
  92. Yellon D. M., Latchman D. S. Stress proteins and myocardial protection. J Mol Cell Cardiol. 1992 Feb;24(2):113–124. doi: 10.1016/0022-2828(92)93148-d. [DOI] [PubMed] [Google Scholar]
  93. Yokoyama T., Vaca L., Rossen R. D., Durante W., Hazarika P., Mann D. L. Cellular basis for the negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian heart. J Clin Invest. 1993 Nov;92(5):2303–2312. doi: 10.1172/JCI116834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Zelenka P. S. Proto-oncogenes in cell differentiation. Bioessays. 1990 Jan;12(1):22–26. doi: 10.1002/bies.950120105. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES