Old and New Mediators in Sepsis The Enigma Is Not Yet Resolved

  • M. Antonelli
  • M. Passariello
Conference paper


Sepsis may be defined as a systemic inflammatory response to an infection. The syndrome is characterized by alterations in temperature, leukocytosis, hypotension, hypoperfusion with cellular injury and organ failure often resulting in death.


Disseminate Intravascular Coagulation Disseminate Intravascular Coagulation Intracellular Adhesion Molecule Experimental Endotoxemia Meningococcal Septic 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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kreger BE, Craven DE, McCabe WR (1980) Gram negative bacteremia IV. Re-evaluation of clinical features and treatments in 612 patients. Am J Med 68:344–355PubMedCrossRefGoogle Scholar
  2. 2.
    Fujishima S, Aikawa N (1995) Neutrophil-mediated tissue injury and its modulation. Intensive Care Med 21:277–285PubMedCrossRefGoogle Scholar
  3. 3.
    Levi M, ten Cate H, van der Poll T, van Deventer SJH (1993) Pathogenesis of disseminated intravascular coagulation in sepsis. JAMA 270:975–979PubMedCrossRefGoogle Scholar
  4. 4.
    Gamble JR, Harlan JM, Klebanoff SJ, Vadas MA (1985) Stimulation of the adherence of neutrophils to umbilical vein endothelium by recombinant TNF. Proc Natl Acad Sci USA 82: 8667–8671PubMedCrossRefGoogle Scholar
  5. 5.
    Verheij M, Bose R, Xin HL et al (1996) Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 380:75–79PubMedCrossRefGoogle Scholar
  6. 6.
    Michie HR, Manogue KR, Spriggs DR et al (1988) Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med 318:1481–1486PubMedCrossRefGoogle Scholar
  7. 7.
    Matrich GD, Danner RL, Ceska M, Suffredini AF (1991) Detection of IL-8 and TNF in normal humans after intravenous endotoxin. The effect of anti-inflammatory agents. J Exp Med 173:1021–1024CrossRefGoogle Scholar
  8. 8.
    Sylvester I, Cuffredini AF, Boujoukos AJ et al (1993) Neutrophil attractant protein 1 and monocyte chemoattractant protein 1 in human serum. J Immunol 151:3292–3298PubMedGoogle Scholar
  9. 9.
    Van der Poll T, Levi M, van Deventer SHJ et al (1994) Differential effects of anti-TNF antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. Blood 83:446–451PubMedGoogle Scholar
  10. 10.
    Van der Poll, Levi M, Hack Ce et al (1994) EUmination of IL-6 attenuates coagulation activation in experimental endotoxemia in chimpazees. J Exp Med 179:1253–1259PubMedCrossRefGoogle Scholar
  11. 11.
    Raponi G, Antonelli M, Gaeta G et al (1992) TNF in serum and in BAL of patients at risk for ARDS. J Crit Care 7:183–188CrossRefGoogle Scholar
  12. 12.
    Finn A, Naik S, Klein N et al (1993) Interleukin-8 release and neutrophil degranulation after paediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg 105:234–241PubMedGoogle Scholar
  13. 13.
    Bauer J, Herrmann F (1991) Interleukin-6 in clinical medicine. Ann Hematol 62:203–207PubMedCrossRefGoogle Scholar
  14. 14.
    Antonelli M, Raponi GM, Martino P et al (1995) High IL-6 serum levels are associated with septic shock with severe leukopenia due to malignancies. Scand J Infect Dis 27:381–384PubMedCrossRefGoogle Scholar
  15. 15.
    Suffredini AF, Reda D, Banks SM et al (1995) Effects of recombinant dimeric TNF receptors on human inflammatory responses following intravenous endotoxin administration. J Immunol 155:5038–5045PubMedGoogle Scholar
  16. 16.
    Von der Mohlen MAM, Kimmings NA, Wedel N et al (1995) Inhibition of endotoxin-induced cytokine release and neutrophil activation in human using a recombinant endotoxin binding protein (rBPI23). J Infect Dis 172:144–151PubMedCrossRefGoogle Scholar
  17. 17.
    Gorgen I, Härtung T, Leist M et al (1991) Granulocyte colony-stimulating factor treatment protects rodents against LPS-induced toxicity via suppression of systemic TNF alpha. J Immunol 149:918–924Google Scholar
  18. 18.
    Sartorelli KH, Silver GM, Gamelli RL (1991) The effect of C-GSF upon bum-induced defective neutrophil Chemotaxis. J Trauma 31:523–529PubMedCrossRefGoogle Scholar
  19. 19.
    Nelson S, Parkas S, Fotheringham N et al (1996) Filgrastin in the treatment of hospitalized patients with community acquired pneumonia. Am J Respir Crit Care Med 153 (abs)Google Scholar
  20. 20.
    Pollmacher T, Korth C, Mullington J et al (1996) Effects of G-CSF on plasma cytokine and cytokine receptor levels and on the vivo host response to endotoxin in healthy men. Blood 87:900–905PubMedGoogle Scholar
  21. 21.
    Derkx B, Marchant A, Goldman M et al (1995) High levels of IL-10 during the initial phases of fulminant meningococcal septic shock. J Infect Dis 171:229–232PubMedCrossRefGoogle Scholar
  22. 22.
    Hun RD, Radwaski E, O’ConneU SM et al (1996) Pharmacokinetics and immunomodulatory properties of intravenous administred recombinant human IL-10 in healthy volunteers. Blood 87:699–705Google Scholar
  23. 23.
    Schmid-Schonbein GW, Usami S, Skalak R et al (1980) The interaction of leukocytes and erythrocytes in capillary and postcapillary vessels. Microvasc Res 19:45–70PubMedCrossRefGoogle Scholar
  24. 24.
    Mayrovitz HN, Rubin R (1985) Leukocyte distribution to arteriolar branches: Dependence on microvascular blood flow. Microvasc Res 29:282–294PubMedCrossRefGoogle Scholar
  25. 25.
    Kishimoto TK, Jutiha MA, Berg EL et al (1989) Neutrophil Mac.l and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science 245:1238–1241PubMedCrossRefGoogle Scholar
  26. 26.
    Anderson DC (1995) The role of Beta 2 integrins and intracellular adhesion molecule type 1 in inflammation. In: Granger DN, Schmid, Schonbein (eds) Physiology and pathophysiology of leukocyte adhesion. 1st edn. Oxford University Press, New York, pp 3–42Google Scholar
  27. 27.
    Windsor ACJ, Walsh CJ, Mullen PG et al (1993) TNF alpha blockade prevents neutrophil CD 18 receptorupregulation and attenuates acute lung injury in porcine sepsis without inhibition of neutrophil oxygen radical generation. J Clin Invest 91:1459–1468PubMedCrossRefGoogle Scholar
  28. 28.
    Pixley RA, de la Cadena R, Page JD et al (1993) The contact system contributes to hypotension, but not to Die in lethal bacteremia. J Clin Invest 91:61–68PubMedCrossRefGoogle Scholar
  29. 29.
    Van der Poll T, Levi M, Hack CE et al (1994) Elimination of IL-6 attenuates coagulation activation in experimental endotoxemia in chimpanzee. J Exp Med 179:1253–1259PubMedCrossRefGoogle Scholar
  30. 30.
    Gawaz M, Dickfeld T, Bogner et al (1997) Platelet function in septic multiple organ dysfunction syndrome. Intensive Care Med 23:379–385PubMedCrossRefGoogle Scholar
  31. 31.
    Hannun YA, Obeid LM (1995) Ceramide: an intracellular signal for apoptosis. Trends Biochem Sei 20:386–401CrossRefGoogle Scholar
  32. 32.
    Wiegmann K, Scheutze K, Machleidt T et al (1994) Functional dichotomy of neutral and acidic sphingomyelinases in TNF signalling. Cell 78:1005–1015PubMedCrossRefGoogle Scholar
  33. 33.
    Teodorczyk-Injeyan JA, Cembrznska-Nowak M, Llani S et al (1995) Immune deficiency following thermal trauma is associated with apoptotic cell death. J Clin Immunol 15:318–328PubMedCrossRefGoogle Scholar
  34. 34.
    Chitnis DC, Dickerson C, Munster AM et al (1996) Inhibition of apoptosis in polymorphonuclear neutrophils from bum patients. J Leuk Biol 59:835–839Google Scholar
  35. 35.
    Bone (1996) Immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response (SIRS) and the multiple organ dysfunction syndrome (MODS). Ann Intem Med 125:680–687Google Scholar

Copyright information

© Springer-Verlag Italia, Milano 1998

Authors and Affiliations

  • M. Antonelli
  • M. Passariello

There are no affiliations available

Personalised recommendations