The Role of TNF in Gram-Negative Sepsis in Baboon

  • H. Redl
  • G. Schlag G
  • J. Davies
  • W. A. Buurman
  • M. Bodmer
Conference paper

Abstract

During sepsis TNF message is expressed and the protein is released both locally and into plasma. Teleologically such cytokine response must be beneficial to the host. However, from a certain threshold level of activation there might be an overactivation and imbalance of the cytokine system, which then tends to be harmful to the host. Cytokines in sepsis occur in sequence, with possible reciprocal amplification or inhibition cascade.

Keywords

Dexamethasone Glucocorticoid Thrombin Peritonitis Corticosterone 

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References

  1. Bahrami S, Redl H, Buurman WA, Schlag G (1992) The influence of xanthine derivative HWA-138 on endotoxin related coagulation disorders — effect in non-sensitized vs D-galactosamine sensitized rats. Thromb Haemost, in pressGoogle Scholar
  2. Bahrami S, Redl H, Leichtfried G, Kober C, Wilfing C, Schlag G (1991b) Beneficial effects of anti-TNF monoclonal antibody (mAb) in endotoxin-induced coagulation disorder in rats. Circ Shock 34:167Google Scholar
  3. Bahrami S, Redl H, Leichtfried G, Yu Y, Schlag G (1992) Similar cytokine but different coagulation response to lipopolysaccharide injection in D-galactosamine sensitized versus non-sensitized rats. SubmittedGoogle Scholar
  4. Bahrami S, Redl H, Schlag G, Buurman WA (1991c) Protective effects of monoclonal antibody (mAB) to tumor necrosis factor (TNF) in experimental endotoxic shock. Oral presentation — 2nd International congress ’The immune consequences of trauma, shock and sepsis — Mechanisms and therapeutic approaches, March 6th – 9th, Munich 1991Google Scholar
  5. Bahrami S, Redl H, Schlag G, Leichtfried G, Ceska M, Strieter RM (1991d) Comparison of the efficacy of different xanthine derivates to reduce endotoxin-induced mortality and/or cytokine production: in vivo and in vitro studies. Circ Shock 34:140Google Scholar
  6. Bahrami S, Schießer A, Redl H, Schlag G (1987) Comparison of different corticosteroids in rat endotoxemia. In: Schlag G, Redl H (eds) First Vienna Shock Forum — Monitoring and treatment of shock. Liss, New York (Progress in Clinical and Biological research, vol 236B), pp 273–286Google Scholar
  7. Beutler B, Cerami A (1987) Cachectin: More than a tumor necrosis factor. N Engl J Med 316:379–385PubMedCrossRefGoogle Scholar
  8. Beutler B, Krochin N, Milsark IW, Luedke C, Cerami A (1986) Control of cachectin (tumor necrosis factor) synthesis: mechanism of endotoxin resistance. Science 232:977–980PubMedCrossRefGoogle Scholar
  9. Beutler B, Milsark IW, Cerami AC (1985b) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229:869–871PubMedCrossRefGoogle Scholar
  10. Ceska M, Effenberger F, Peichl P, Pursch E (1989) Purification and characterization of monoclonal and polyclonal antibodies to neutrophil activating peptide (NAP-1). The development of highly sensitive ELISA-methods for the determination of NAP-1 and anti-NAP-1 antibodies. Poster presented at the 2nd International Workshop on Cytokines, Hilton Head, SC, DecemberGoogle Scholar
  11. Doherty GM, Jensen JC, Alexander HR, Buresh GM, Norton JA (1991) Pentoxifylline suppression of tumor necrosis factor gene transcription. Surgery 110:192–198PubMedGoogle Scholar
  12. Emerson TEjr, Lindsey DC, Jesmok GJ, Duerr ML, Fournel MA (1992) Efficacy of monoclonal antibody against tumor necrosis factor alpha in an endotoxemic baboon model. Circ Shock in pressGoogle Scholar
  13. Emori T, Hirata Y, Ohta K, Shichiri M, Shimokado K, Marumo F (1991) Concomitant secretion of big endothelin and its C-terminal fragment from human and bovine endothelial cells. Biochem Biophys Res Commun 162:217–223CrossRefGoogle Scholar
  14. Fernandez-Botran R (1991) Soluble cytokine receptors: their role in immunoregulation. Faseb J 5:2567–2574PubMedGoogle Scholar
  15. Feuerstein G, Hallenbeck JM, Vanatta B, Rabinovici R, Perera PY, Vogel SN (1990) Effect of gram negative endotoxin on levels of serum corticosterone TNF alpha circulating blood cells and the survival of rats. Circ Shock 30:265–278PubMedGoogle Scholar
  16. Fong Y, Tracey KJ, Moldawer LL, Hesse DG, Manogue KB, Kenney JS, Lee AT, KUO GC, Allison AC, Lowry SF, Cerami A (1989) Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 and interleukin 6 appearance during lethal bacteremia. J Exp Med 170:1627–1633PubMedCrossRefGoogle Scholar
  17. Fridman EP, Poova VN (1988) Species of the genus papio (cercopithecidae) as subjects of biomedical research: I. Biological basis of experiments on baboons. J Med Primatol 17:291–307PubMedGoogle Scholar
  18. Greisman SE, Hornick RB, Wagner HNjr, Woodward WE, Woodward TE (1969) The role of endotoxin during typhoid fever and tularemia in man. IV. The integrity of the endotoxin tolerance mechanism during infection. J Clin Invest 48:613–617PubMedCrossRefGoogle Scholar
  19. Groenewald van Zyl JJW (1973) The cape chacma baboon in surgical research. In: Bourne GH (ed) Nonhuman primates and medical research, Academic Press, New York Londeon, pp 269–279Google Scholar
  20. Hinshaw LB, Tekamp-Olson P,Chang ACK, Lee PA, Taylor FBjr, Murray CK, Peet GT, Emerson TEjr, Passey RB, Kuo GC (1990) Survival of primates in LD100 septic shock following therapy with antibody to tumor necrosis factor (TNFa). Circ Shock 30:279–292PubMedGoogle Scholar
  21. Hitchcock CR (1969) Experimental surgery in primates and in standard laboratory animals: a comparative survey. Ann NY Acad Sci 162:393–403PubMedCrossRefGoogle Scholar
  22. Ishii H, Uchiyama H, Kazama M (1991) Soluble thrombomodulin antigen in conditioned medium is increased by damage of endothelial cells. Thromb Haemost 65:618–623PubMedGoogle Scholar
  23. Kourembanas S, Marsden PA, McQuillan LP, Faller DV (1991) Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. J Clin Invest 88:1054–1057PubMedCrossRefGoogle Scholar
  24. Kunkel SL, Spengler M, May MA, Spengler R, Larrick J, Remick D (1988) Prostaglandin E2 regulates macrophage derived tumor necrosis factor gene expression. J Biol Chem 263:5380–5384PubMedGoogle Scholar
  25. Kriegler M, Perez C, DeFay K, Albert I, Lu SD (1988) A novel form a human TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell 53:45–53PubMedCrossRefGoogle Scholar
  26. Mathison J, Wolfson E, Ulevitch R (1988) Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits. J Clin Invest 81:1925–1937PubMedCrossRefGoogle Scholar
  27. Nawroth PP, Bank I, Handley D, Cassimeris J, Chess L, Stern D (1989) Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med 163:1363–1375CrossRefGoogle Scholar
  28. Nawroth PO, Stern DM (1986) Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 163:740–745PubMedCrossRefGoogle Scholar
  29. Nute PE, Mahoney WC (1979) Complete sequence of the chain from the fetal hemoglobin of the baboon, papio cynocephalus. Hemoglobin 3:399–410PubMedCrossRefGoogle Scholar
  30. Olsson I, Lanatz M, Nilsson E, Peetre C, Thysell H, Grubb A, Adolf G (1989) Isolation and characterization of a tumor necrosis factor binding protein from urine. Eur J Haematol 42:270–275PubMedCrossRefGoogle Scholar
  31. Philipp J, Offner F, Declerck PJ, Leroux-Roels G,Vogelaers D, Baele G, Collen D (1991) Fibrinolysis and coagulation in patients with infectious disease and sepsis. Thromb Haemost 65:291–295Google Scholar
  32. Pralong G, Calandra T, Glauser MP, Schellekens J, Verherherhoef J, Bachmann F, Kruithof EKO (1989) Plasminogen activator inhibitor 1: A new prognostic marker in septic shock. Thromb Haemost 61:459–462PubMedGoogle Scholar
  33. Redl H, Schlag G, Bahrami S, Davies J, Waage A, Ceska M, Buurman W, Adolf G (1992) Cytokine network in trauma and sepsis. 1. TNF and IL-8. In: Schlag G, Redl H (eds) Pathophysiology of Shock, Sepsis and Organ Failure, Springer, Heidelberg in pressGoogle Scholar
  34. Redl H, Schlag G, Bahrami S, Schade U, Ceska M, Stütz P (1991a) Plasma neutrophil-activating peptide-1/interleukin-8 and neutrophil elastase in a primate bacteremia model. J Infect Dis 164:383–388PubMedCrossRefGoogle Scholar
  35. Redl H, Schlag G, Davies J, Haller I (1992) No tolerance induction by multiple application of live E. coli in baboons (Abstract). Circ. Shock 37:39Google Scholar
  36. Redl H, Schlag G, Dinges HP, Buurman WA, Ceska M, Davies J (1991b) TNF-dependent ELAM-1 expression and IL-8 release in baboon septicemia. (Abstract) Circ Shock 34:92Google Scholar
  37. Sawdey M, Poder TJ, Loskutoff DJ (1991) Regulation of type 1 plasminogen activator inhibitor gene expression in cultured bovine aortic endothelial cells; induction by transforming growth factor-beta, lipopolysaccharide, and tumor necrosis factor. J Biol Chem 264:10396–10401Google Scholar
  38. Schlag G, Redl H, Davies J (1991) TNF-antibodies (CB0006) in a subchronic septic model in baboons to prevent multi-organ failure (Abstract). Circ Shock 34:164–165Google Scholar
  39. Schlag G, Redl H, van Vuuren CJJ, Davies J (1992a) Hyperdynamic sepsis in baboons. II. Relation of organ damage to severity of sepsis evaluated by a newly developed morphological scoring system. Circ Shock in pressGoogle Scholar
  40. Schlag G, Redl H, Davies J, Bodmer M, Foulkes R (1992b) Humanized TNF-antibodies in a subchronîc septic model in baboons with single bacterial challenge to improve survival and to prevent multi-organ failure (MOF). Circ Shock 37:52–53Google Scholar
  41. Strieter RM, Phan SH, Showell HJ (1989) Monokine-induced neutrophil chemotactic factor gene expression in human fibroblasts. J Biol Chem 264:10621–10626PubMedGoogle Scholar
  42. Tannenbaum CS, Hamilton TA (1989) Lipopolysaccharide-induced gene expression in murine peritoneal macrophages is selectively suppressed by agents that elevate intracellular cAMP. J Immunol 142:1274–1280PubMedGoogle Scholar
  43. Taylor FB, Esmon CT, Hinshaw LB (1990) Summary of staging mechanism and intervention studies in the baboon model of E coli sepsis. J Trauma 30:S197–S207Google Scholar
  44. Tracey KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC, Lowry SF, Cerami A (1987) Anticachectin/TNF monoclonal antibodies prevent septic shock during experimental bacteremia. Nature 330:662–664PubMedCrossRefGoogle Scholar
  45. van der Poll T, Büller HR, ten Cate H, Wortel CH, Bauer KA, van Deventer SJH, Hack CE, Sauerwein HP, Rosenberg RD, ten Cate JW (1990) Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 322:1622–1627PubMedCrossRefGoogle Scholar
  46. van der Poll T, Levi M, Büller HR, van Deventer SJH, deBoer JP, Hack CE, tenCate JW (1991) Fibrinolytic response to tumor necrosis factor in healthy subjects. J Exp Med 174:729–732PubMedCrossRefGoogle Scholar
  47. Van Zee KJ, DeForge LE, Fischer E, Marano MA, Kenney JS, Remick DG, Lowry SF, Moldawer LL (1991) IL-8 in septic shock, endotoxemia, and after IL-1 administration. J Immunol 146:3478–3480PubMedGoogle Scholar
  48. Waage A (1987) Production and clearance of tumor necrosis factor in rats exposed to endotoxin and dexamethasone. Clin Immunol Immunopathol 45:348–355PubMedCrossRefGoogle Scholar
  49. Waage A, Bakke O (1988) Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharide-stimulated human monocytes. Immunol 63:299–302Google Scholar
  50. Waage A, Sorensen M, Stordal B (1990) Differential effect of oxpentifylline on tumour necrosis factor and interleukin-6 production. Lancet 335:543PubMedCrossRefGoogle Scholar
  51. Yanagisawa M, Kurihara H (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415PubMedCrossRefGoogle Scholar
  52. Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheimer JJ, Leonard EJ (1987) Purification of a human monocyte derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci USA 84:9233–9237PubMedCrossRefGoogle Scholar
  53. Zabel P, Schönharting MM. Wolter DT, Schade UF (1989) Oxpentifylline in endotoxaemia. Lancet 11:1474–1477CrossRefGoogle Scholar
  54. Zuckerman SH, Shellhaas J, Butler LD (1989) Differential regulation of lipopolysaccharide induced interleukin 1 and tumor necrosis factor synthesis: effects of endogenous and exogenous glucocorticoids and the role of the pituitary adrenal axis. Eur J Immunol 19:301–305PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • H. Redl
    • 1
  • G. Schlag G
    • 1
  • J. Davies
    • 2
  • W. A. Buurman
    • 3
  • M. Bodmer
    • 4
  1. 1.Ludwig Boltzmann Institute for Experimental and Clinical TraumatologyViennaAustria
  2. 2.Roodeplaat Research LaboratoriesPretoriaSouth Africa
  3. 3.Department of SurgeryUniversity of LimburgThe Netherlands
  4. 4.Molecular ImmunologyCelltechSloughUK

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