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Emerging Evidence of a More Complex Role for Proinflammatory and Antiinflammatory Cytokines in the Sepsis Response

  • Lyle L. Moldawer
  • Rebecca M. Minter
  • John E. RectenwaldIII
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Abstract

Since the original discovery and cloning of tumor necrosis factor-α (TNFα) and interleukin-1 (IL-1), our understanding of the underlying role that these and other cytokines play in the sepsis response has greatly evolved.The original concept that the sepsis response is a result of a linear cytokine cascade induced by TNFα and IL-1 has given way to the appreciation that sepsis syndromes often result from a more complex interplay between proinflammatory cytokines, antiinflammatory cytokines, and cytokine antagonists. The proinflammatory cytokine-dominated, systemic inflammatory response syndrome is likely an episodic or transient occurrence; and many septic patients present with a compensatory antiinflammatory cytokine response dominated by the release of antiinflammatory cytokines and cytokine antagonists, leading to immune suppression. There is also growing appreciation that other members of the TNFα superfamily, including Fas ligand (FasL) and glucocorticoids, play an increasingly important role in the loss of immune cells during sepsis through apoptotic processes. The cytokine component of the innate immune response to sepsis plays a complex role not only in the inflammatory response syndrome but also in determining the nature and magnitude of the acquired immune response.

Keywords

Systemic Inflammatory Response Syndrome Sepsis Syndrome Tumor Necrosis Factor Family Cytokine Antagonist Endotoxemic Shock 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Pennica D, Nedwin GE, Hayflick JS, et al: Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 1984; 312: 724–729.PubMedCrossRefGoogle Scholar
  2. 2.
    Pennica D, Hayflick JS, Bringman TS, Palladino MA, Goeddel DV: Cloning and expression in Escherichia coliof the cDNA for murine tumor necrosis factor. Proc Natl Acad Sci USA 1985; 82: 6060–6064.PubMedCrossRefGoogle Scholar
  3. 3.
    Lomedico PT, Gubler U, Hellmann CP, et al: Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. Nature 1984; 312: 458–462.PubMedCrossRefGoogle Scholar
  4. 4.
    Auron PE, Rosenwasser LJ, Mateushima K, et al: Human and murine interleukin 1 poisess sequence and structural similarities. J Mol Cell Immunol.1985; 2: 169–177.PubMedGoogle Scholar
  5. 5.
    Beutler B, Greenwald D, Hulmes JD, et al: Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature 1985; 316: 552–554.PubMedCrossRefGoogle Scholar
  6. 6.
    Tracey KJ, Beutler B, Lowry SF, et al: Shock and tissue injury induced by recombinant human cachectin. Science 1986; 234: 470–474.PubMedCrossRefGoogle Scholar
  7. 7.
    Ohlsson K, Bjork P, Bergenfeldt M, Hageman R, Thompson RC: Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature 1990; 348: 550–552.PubMedCrossRefGoogle Scholar
  8. 8.
    Fischer E, Marano MA, Van Zee KJ, et al: Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coliseptic shock, but fails to alter host responses to sublethal endotoxemia. J Clin Invest 1992; 89: 1551–1557.PubMedCrossRefGoogle Scholar
  9. 9.
    Zeni F, Freeman B, Natanson C: Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment [editorial;comment]. Crit Care Med 1997; 25: 1095–1100.PubMedCrossRefGoogle Scholar
  10. 10.
    Baue AE: Multiple organ failure, multiple organ dysfunction syndrome, and systemic inflammatory response syndrome: why no magic bullets? Arch Surg 1997; 132: 703–707.PubMedCrossRefGoogle Scholar
  11. 11.
    Cain BS, Meldrum DR, Harken AH, McIntyre RC Jr: The physiologic basis for anticytokine clinical trials in the treatment of sepsis. J Am Coll Surg 1998; 186: 337–350.PubMedCrossRefGoogle Scholar
  12. 12.
    Vincent JL: Search for effective immunomodulating strategies against sepsis [comment]. Lancet 1998; 351: 922–923.PubMedGoogle Scholar
  13. 13.
    Welborn MB III, van Zee K, Edwards PD, et al: A human tumor necrosis factor p75receptor agonist stimulates in vitro T cell proliferation but does not produce inflammation or shock in the baboon. J Exp Med 1996; 184: 165–171.PubMedCrossRefGoogle Scholar
  14. 14.
    Tracey KJ, Lowry SF, Fahey TJ, et al: Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg Gynecol Obstet 1987; 164: 415–422.PubMedGoogle Scholar
  15. 15.
    Vander Poll T, Romijn JA, Endert E, Borm JJ, Buller HR, Sauerwein HP: Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans. Am J Physiol 1991; 261: E457–E465.PubMedGoogle Scholar
  16. 16.
    Vander Poll T, Jansen J, Levi M, et al: Regulation of interleukin 10 release by tumor necrosis factor in humans and chimpanzees. J Exp Med 1994; 180: 1985–1988.PubMedCrossRefGoogle Scholar
  17. 17.
    Vander Poll T, Jansen PM, Van Zee KJ, et al: Tumor necrosisfactor-alpha induces activation of coagulation and fibrinolysis inbaboons through an exclusive effect on the p55 receptor. Blood 1996; 88: 922–927.PubMedGoogle Scholar
  18. 18.
    VanZee KJ, Stackpole SA, Montegut WJ, et al: A human tumor necrosis factor (TNF) αmutant that binds exclusively to the p55 TNF receptor produces toxicity in the baboon. J Exp Med 1994; 179: 1185–1191.PubMedCrossRefGoogle Scholar
  19. 19.
    Fong Y, Tracey KJ, Moldawer LL, et al: Antibodies to cachec—tin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia. J Exp Med 1989; 170: 1627–1633.PubMedCrossRefGoogle Scholar
  20. 20.
    Van Zee KJ, Moldawer LL, Oldenburg HS, et al: Protection against lethal Escherichia colibacteremia in baboons (Papio anubis)by pretreatment with a 55-kDa TNF receptor (CD120a)-Ig fusion protein, Ro 45-2081. J Immunol 1996; 156: 2221–2230.PubMedGoogle Scholar
  21. 21.
    Jansen J, vander Poll T, Levi M, et al: Inhibition of the release of soluble tumor necrosis factor receptors in experimental endotox-emia by an anti-tumor necrosis factor-αantibody. J Clin Immunol 1995; 15: 45–50.PubMedCrossRefGoogle Scholar
  22. 22.
    Vander Poll T, van Deventer SJ, ten Cate H, Levi M, ten Cate JW: Tumor necrosis factor is involved in the appearance of interleukin-1 receptor antagonist in endotoxemia. J Infect Dis 1994; 169: 665–667.PubMedCrossRefGoogle Scholar
  23. 23.
    Remick D, Manohar P, Bolgos G, Rodriguez J, Moldawer L, Wollenberg G: Blockade of tumor necrosis factor reduces lipo-polysaccharide lethality, but not the lethality of [ceccal ligation and puncture]. Shock 1995; 4: 89–95.PubMedCrossRefGoogle Scholar
  24. 24.
    Bagby GJ, Plessala KJ, Wilson LA, Thompson JJ, Nelson S: Divergent efficacy of antibody to tumor necrosis factor-alpha in intravascular and peritonitis models of sepsis. J Infect Dis 1991; 163: 83–88.PubMedCrossRefGoogle Scholar
  25. 25.
    Echtenacher B, Falk W, Mannel DN, Krammer PH: Requirement of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis. J Immunol 1990; 145: 3762–3766.PubMedGoogle Scholar
  26. 26.
    Bone RC: Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med 1996; 24: 1125–1128.PubMedCrossRefGoogle Scholar
  27. 27.
    Van Zee KJ, Kohno T, Fischer E, Rock CS, Moldawer LL, Lowry SF: Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alpha in vitro and in vivo. Proc Natl Acad Sci USA 1992; 89: 4845–4849.PubMedCrossRefGoogle Scholar
  28. 28.
    Fisher CJ Jr, Dhainaut J-FA, Opal SM, et al: Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome: results from a randomized, double-blind, placebo-controlled trial. JAMA 1994; 271: 1836–1843.PubMedCrossRefGoogle Scholar
  29. 29.
    Pruitt JH, Welborn MB, Edwards PD, et al: Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome. Blood 1996; 87: 3282–3288.PubMedGoogle Scholar
  30. 30.
    Clark MA, Hank LD, Connolly AB, et al: Effect of a chimeric antibody to tumor necrosis factor-alpha on cytokine and physiologic responses in patients with severe sepsis—a randomized, clinical trial Crit Care Med 1998; 26: 1650–1659.CrossRefGoogle Scholar
  31. 31.
    Bone RC: Immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS). Ann Intern Med 1996; 125: 680–687.PubMedGoogle Scholar
  32. 32.
    Derkx B, Marchant A, Goldman M, Bijlmer R, van Deventer S: High levels of interleukin-10 during the initial phase of fulminant meningococcal septic shock. J Infect Dis 1995; 171: 229–232.PubMedCrossRefGoogle Scholar
  33. 33.
    Marchant A, Deviere J, Byl B, de Groote D, Vincent J-L, Goldman M: Interleukin-10 production during septicaemia. Lancet 1994; 343: 707–708.PubMedCrossRefGoogle Scholar
  34. 34.
    Neidhardt R, Keel M, Steckholzer U, et al: Relationship of interleukin-10 plasma levels to severity of injury and clinical outcome in injured patients. J Trauma 1997; 42: 863–870.PubMedCrossRefGoogle Scholar
  35. 35.
    Van Dissel JT, Van Sangevelde P, Westendorp RG, et al: Antiinflammatory cytokine profile and mortality in febrile patients. Lancet 1998; 351: 950–953.PubMedCrossRefGoogle Scholar
  36. 36.
    Cassatella MA, Meda L, Bonora S, Ceska M, Constantin G: Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes: evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide. J Exp Med 1993; 178: 2207–2211.PubMedCrossRefGoogle Scholar
  37. 37.
    Kasama T, Strieter RM, Lukacs NW, Lincoln PM, Burdick MD, Kunkel SL: Interleukin-10 expression and chemokine regulation during the evolution of murine type II collagen-induced arthritis. J Clin Invest 1995; 95: 2868–2876.PubMedCrossRefGoogle Scholar
  38. 38.
    Fong YM, Marano MA, Moldawer LL, et al: The acute splanchnic and peripheral tissue metabolic response to endotoxin in humans. J Clin Invest 1990; 85: 1896–1904.PubMedCrossRefGoogle Scholar
  39. 39.
    Fischer E, Van Zee KJ, Marano MA, et al: Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease. Blood 1992; 79: 2196–2200.PubMedGoogle Scholar
  40. 40.
    van Zee KJ, Coyle SM, Calvano SE, et al: Influence of IL-1 receptor blockade on the human response to endotoxemia. J Immunol 1995; 154: 1499–1507.PubMedGoogle Scholar
  41. 41.
    Calvano SE, Thompson WA, Coyle SN, et al: Changes in monocyte and soluble tumor necrosis factor receptors during endotoxemia or sepsis. Surg Forum 1993; 44: 114–116.Google Scholar
  42. 42.
    Moore KW, O’Garra A, de Waal Malefyt R, Vieira P, Mosmann TR: Interleukin-10. Annu Rev Immunol 1993; 11: 165–190.PubMedCrossRefGoogle Scholar
  43. 43.
    de Waal Malefyt R, Haanen J, Spits H, et al: Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 1991; 174: 915–924.PubMedCrossRefGoogle Scholar
  44. 44.
    Wanidworanun C, Strober W: Predominant role of tumor necrosis factor alpha in human monocyte IL-10 synthesis. J Immunol 1996; 151: 6853–6861.Google Scholar
  45. 45.
    Cassatella MA, Meda L, Gasperini S, Calzetti F, Bonora S: Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation. J Exp Med 1994; 179: 1695–1699.PubMedCrossRefGoogle Scholar
  46. 46.
    Wang P, Wu P, Anthes JC, Siegel MI, Egan RW, Billah MM: Interleukin-10 inhibits interleukin-8 production in human neutrophils. Blood 1994; 83: 2678–2683.PubMedGoogle Scholar
  47. 47.
    van der Poll T, Jansen PM, Montegut WJ, et al: Effects of IL-10 on systemic inflammatory responses during sublethal primate endotoxemia. J Immunol 1997; 158: 1971–1975.PubMedGoogle Scholar
  48. 48.
    Howard M, Muchamuel T, Andrade S, Menon S: Interleukin 10 protects mice from lethal endotoxemia. J Exp Med 1993; 177: 1205–1208.PubMedCrossRefGoogle Scholar
  49. 49.
    Gerard C, Bruyns C, Marchant A, et al: Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. J Exp Med 1993; 177: 547–550.PubMedCrossRefGoogle Scholar
  50. 50.
    Huhn RD, Radwanski E, O’Connell SM, et al: Pharmacokineticsand immunomodulatory properties of intravenously administeredrecombinant human interleukin-10 in healthy volunteers. Blood 1996; 87: 699–705.PubMedGoogle Scholar
  51. 51.
    Chernoff AE, Granowitz EV, Shapiro L, et al: A randomized, controlled trial of IL-10 in humans: inhibition of inflammatory cytokine production and immune responses. J Immunol 1995; 154: 5492–5499.PubMedGoogle Scholar
  52. 52.
    Standiford TJ, Strieter RM, Lukacs NW, Kunkel SL: Neutralization of IL-10 increases lethality in endotoxemia: cooperative effects of macrophage inflammatory protein-2 and tumor necrosis factor. J Immunol 1995; 155: 2222–2229.PubMedGoogle Scholar
  53. 53.
    van der Poll T, Marchant A, Buurman WA, et al: Endogenous IL-10 protects mice from death during septic peritonitis. J Immunol 1995; 155: 5397–5401.PubMedGoogle Scholar
  54. 54.
    Hess PJ, Seeger JM, Huber TS, et al: Exogenously administered interleukin-10 decreases pulmonary neutrophil infiltration in a tumor necrosis factor dependent model of acute visceral ischemia. J Vasc Surg 1997; 26: 113–118.PubMedCrossRefGoogle Scholar
  55. 55.
    Engles RE, Huber TS, Zander DS, et al: Exogenous human recombinant interleukin-10 attenuates hindlimb ischemi-reperfusion injury. J Surg Res 1997; 69: 425–428.PubMedCrossRefGoogle Scholar
  56. 56.
    Kelly JL, Lyons A, Soberg CC, Mannick JA, Lederer JA: Antiinterleukin-10 antibody restores burn-induced defects in T-cell function. Surgery 1997; 122: 146–152.PubMedCrossRefGoogle Scholar
  57. 57.
    Song GY, Chung CS, Schwacha MG, Jarrar D, Chaudry IH, Ayala A: Splenic immune suppression in sepsis: A role for IL-10-induced changes in P38 MAPK signaling. J Surg Res 1999; 83: 36–43.PubMedCrossRefGoogle Scholar
  58. 58.
    Steinhauser ML, Hogaboam CM, Kunkel SL, Lukacs NW, Strieter RM, Standiford TJ: IL-10 is a major mediator of sepsis-induced impairment in lung antibacterial host defense. J Immunol 1999; 162: 392–399.PubMedGoogle Scholar
  59. 59.
    Van der Poll T, Marchant A, Keogh CV, Goldman M, Lowry SF: Interleukin-10 impairs host defense in murine pneumococcal pneumonia. J Infect Dis 1996; 174: 994–1000.PubMedCrossRefGoogle Scholar
  60. 60.
    Keystone E, Wherry J, Grint P: IL-10 as a therapeutic strategy in the treatment of rheumatoid arthritis. Rheum Dis Clin North Am 1998; 24: 629–639.PubMedCrossRefGoogle Scholar
  61. 61.
    Van Montfrans C, Camoglio L, van Deventer SJ: Immunotherapy of Crohn’s disease. Mediators Inflamm 1998; 7: 149–152.PubMedCrossRefGoogle Scholar
  62. 62.
    Ksontini R, MacKay SL, Moldawer LL: Revisiting the role of tumor necrosis factor alpha and the response to surgical injury and inflammation. Arch Surg 1998; 133: 558–567.PubMedCrossRefGoogle Scholar
  63. 63.
    Solorzano CC, Ksontini R, Pruitt JH, et al: Involvement of 26-kDa cell-associated TNF-alpha in experimental hepatitis and exacerbation of liver injury with a matrix metalloproteinase inhibitor. J Immunol 1997; 158: 414–419.PubMedGoogle Scholar
  64. 64.
    Kusters S, Tiegs G, Alexopoulou L, et al: In vivo evidence for a functional role of both tumor necrosis factor (TNF) receptors and transmembrane TNF in experimental hepatitis. Eur J Immunol 1997; 27: 2870–2875.PubMedCrossRefGoogle Scholar
  65. 65.
    Alexopoulou L, Pasparakis M, Kollias G: A murine transmembrane tumor necrosis factor (TNF) transgene induces arthritis by cooperative p55/p75 TNF receptor signaling. Eur J Immunol 1997; 27: 2588–2592.PubMedCrossRefGoogle Scholar
  66. 66.
    Mariani SM, Matiba B, Baumler C, Krammer PH: Regulation of cell surface APO-1/Fas (CD95) ligand expression by metallopro-teases. Eur J Immunol 1995; 25: 2303–2307.PubMedCrossRefGoogle Scholar
  67. 67.
    Schneider P, Holler N, Bodmer JL, et al: Conversion of membrane-bound Fas (CD95) ligand to its soluble form is associated with downregulation of its proapoptotic activity and loss of liver toxicity. J Exp Med 1998; 187: 1205–1213.PubMedCrossRefGoogle Scholar
  68. 68.
    Ksontini R, Colagiovanni DB, Josephs MD, et al: Disparate roles for TNF-alpha and Fas ligand in eoncanavalin A-induced hepatitis. J Immunol 1998; 160: 4082–4089.PubMedGoogle Scholar
  69. 69.
    Tannahill CL, Fukuzuka K, Marum T, et al: Discordant TNF-alpha supefamily expression in bacterial peritonitis and endotoxe-mic shock. Surgery 1999; 126: 349–357.PubMedCrossRefGoogle Scholar
  70. 70.
    Griffith TS, Lynch DH: TRAIL: a molecule with multiple receptors and control mechanisms. Curr Opin Immunol 1998; 10: 559–563.PubMedCrossRefGoogle Scholar
  71. 71.
    Hiramatsu M, Hotchkiss RS, Karl IE, Buchman TG: Cecal ligation and puncture (CLP) induces apoptosis in thymus, spleen, lung, and gut by an endotoxin and TNF-independent pathway. Shock 1997; 7: 247–253.PubMedCrossRefGoogle Scholar
  72. 72.
    Ayala A, Herdon CD, Lehman DL, Ayala CA, Chaudry IH: Differential induction of apoptosis in lymphoid tissues during sepsis: variation in onset, frequency, and the nature of the mediators. Blood 1996; 87: 4261–4275.PubMedGoogle Scholar
  73. 73.
    Kondo T, Suda T, Fukuyama H, Adachi M, Nagata S: Essential roles of the Fas ligand in the development of hepatitis. Nat Med 1997; 3: 409–413.PubMedCrossRefGoogle Scholar
  74. 74.
    Fukuzuka K, Rosenberg JJ, Gaines GC, et al: Caspase-3 dependent organ apoptosis early after burn injury [abstract]. Ann Surg 1999; 229: 851–858.PubMedCrossRefGoogle Scholar
  75. 75.
    Hotchkiss RS, Swanson PE, Cobb JP, Jacobson A, Buchman TG, Karl IE: Apoptosis in lymphoid and parenchymal cells during sepsis: a findings in normal and T-and B-cell-deficient mice. Crit Care Med 1997; 25: 1298–1307.PubMedCrossRefGoogle Scholar
  76. 76.
    Ayala A, Urbanich MA, Herdon CD, Chaudry IH: Is sepsis-induced apoptosis associated with macrophage dysfunction? J Trauma 1996; 40: 568–573.PubMedCrossRefGoogle Scholar
  77. 77.
    Ayala A, Xin XY, Ayala CA, et al: Increased mucosal B-lymphocyte apoptosis during polymicrobial sepsis is a Fas ligand but not an endotoxin-mediated process. Blood 1998; 91: 1362–1372.PubMedGoogle Scholar
  78. 78.
    Hotchkiss RS, Swanson PE, Knudson CM, et al: Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. J Immunol 1999; 162: 4148–4156.PubMedGoogle Scholar
  79. 79.
    Hotchkiss RS, Swanson PE, Freeman BD, et al: Apoptotic cell death in patients with sepsis, shock and multiple organ dysfunction [abstract]. Crit Care Med 1999; 27: 1230–1251.PubMedCrossRefGoogle Scholar
  80. 80.
    Nakamura M, Yagi H, Ishii T, et al: DNA fragmentation is not the primary event in glucocorticoid-induced thymocyte death in vivo. Eur J Immunol 1997; 27: 999–1004.PubMedCrossRefGoogle Scholar
  81. 81.
    Alam A, Braun MY, Hartgers F, et al: Specific activation of the cysteine protease CPP32 during the negative selection of T cells in the thymus. J Exp Med 1997; 186: 1503–1512.PubMedCrossRefGoogle Scholar
  82. 82.
    Clayton LK, Ghendler Y, Mizoguchi E, et al: T-cell receptor ligation by peptide/MHC induces activation of a caspase in immature thymocytes: the molecular basis of negative selection. EMBOJ 1997; 16: 2282–2293.CrossRefGoogle Scholar
  83. 83.
    Kriegler M, Perez C, DeFay K, Albert I, Lu SD: A novel form of TNF/cachetin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell 1988; 53: 45–53.PubMedCrossRefGoogle Scholar
  84. 84.
    Grell M, Douni E, Wajant H, et al: The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell 1995; 83: 793–802.PubMedCrossRefGoogle Scholar
  85. 85.
    Keogh C, Fong Y, Marano MA, et al: Identification of a novel tumor necrosis factor alpha/cachectin from the livers of burned and infected rats. Arch Surg 1990; 125: 79–84.PubMedCrossRefGoogle Scholar
  86. 86.
    Moss ML, Catherine-Jin SL, Milla ME, et al: Cloning of a disintegrin metalloproteinase that processes precursor tumor-necrosis factor-α Nature 1997; 385: 733–736.PubMedCrossRefGoogle Scholar
  87. 87.
    Tartaglia LA, Pennica D, Goeddel DV: ligand passing: the 75-kDa tumor necrosis factor (TNI) receptor recruits TNF for signaling by the 55-kDa TNF receptor. J Biol Chem 1993; 268: 18542–18548.PubMedGoogle Scholar
  88. 88.
    Aderka D, Engelmann H, Maor Y, Brakebusch C, Wallach D: Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med 1992; 175: 323–329.PubMedCrossRefGoogle Scholar
  89. 89.
    Solorzano CC, Ksontini R, Pruitt JH, et al: A matrix metalloproteinase inhibitor prevents processing of TNF-alpha and abrogates endotoxin induced lethality. Shock 1997; 7: 427–431.PubMedCrossRefGoogle Scholar
  90. 90.
    Solorzano CC, Kaibara A, Hess PJ, et al: Pharmacokinetics, immunogenidty, and efficacy of dimeric TNFR binding proteins inhealthy and bacteremic baboon. J Appl Physiol 1998; 84: 1119–1130.PubMedGoogle Scholar
  91. 91.
    Georgopolous S, Plows D, Kollias G: Transmembrane TNF is sufficient to induce localized tissue toxicity and chronic inflammatory arthritis in transgenic mice. J Inflamm 1996; 46: 86–97.Google Scholar
  92. 92.
    Eissner G, Kohlhuber F, Grell M, et al: Critical involvement of transmembrane tumor necrosis factor-alpha in endothelial programmed cell death mediated by ionizing radiation and bacterial endotoxin. Blood 1995; 86: 4184–4193.PubMedGoogle Scholar
  93. 93.
    Leist M, Gantner F, Jilg S, Wendel A: Activation of the 55 kDa TNF receptor is necessary and sufficient for TNF-induced liverfailure, hepatocyte apoptosis, and nitrite release. J Immunol 1995; 154: 1307–1316.PubMedGoogle Scholar

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© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Lyle L. Moldawer
  • Rebecca M. Minter
  • John E. RectenwaldIII

There are no affiliations available

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