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Immunostimulation in Sepsis

  • Hans-Dieter Volk
  • Kerstin Wolk
  • Robert Sabat
  • Wolf-Dietrich Döcke
  • Petra Reinke
Part of the Perspectives on Critical Care Infectious Diseases book series (CCID, volume 2)

Abstract

Infectious complications remain a major problem in critically ill patients following trauma, burn injury, major surgery, or septic shock. The high risk of infection in these patients is related in part to the development of an acquired deficiency in host defense. Secondary infections can in turn result in sepsis which if severe is associated with a very high mortality. Over the last two decades our understanding of the pathophysiology of sepsis has progressed considerably. It is now clear that an overwhelming systemic inflammatory response to invasion by bacteria and fungi and/or their toxic products is important in the pathogenesis of SIRS, sepsis and multiple organ failure. Since TNF and IL-1 can mimic sepsis and septic shock in animal models, several recent clinical trials have focused on neutralization of these inflammatory mediators. These trials, however, have had very disappointing results.

Keywords

Septic Shock Septic Patient Lipopolysaccharide Binding Protein Immune Monitoring Apoptotic Material 
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.

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References

  1. 1.
    Natanson C, Hoffman WD, Suffredini AF, Eichacker PQ, Danner RL. Selected treatment strategies for septic shock based on proposed mechanisms of pathogenesis. Ann Intern Med 1994; 120: 771–783.PubMedGoogle Scholar
  2. 2.
    Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med 1997; 25: 1095–1100.PubMedCrossRefGoogle Scholar
  3. 3.
    Döcke WD, Randow F, Syrbe U, Krausch D, Asadullah K, Reinke P, Volk HD, Kox W. Monocyte deactivation in septic patients: restoration by IFN-γ treatment. Nature Med 1997; 3: 678–681.PubMedCrossRefGoogle Scholar
  4. 4.
    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
  5. 5.
    Pfeffer K. Mice deficient for the p55 kD tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 1993; 73: 457–467.PubMedCrossRefGoogle Scholar
  6. 6.
    Jack RS, Fan X, Bernheiden M, Rune G, Ehlers M, Weber A, Kirsch G, Mentel R, Fürll B, Freudenberg M, Schmitz G, Stelter F, Schürt C. Lipopolysaccaride binding protein is required to combat a murine gram-negative bacterial infection. Nature 1997; 389: 742–745.PubMedCrossRefGoogle Scholar
  7. 7.
    Volk HD, Reinke P, Falck P, Staffa G, Briedigkeit H, von Baehr R. Diagnostic value of an immune monitoring program for the clinical management of immunosuppressed patients with septic complications. Clin Transplant 1989; 3: 246–252.Google Scholar
  8. 8.
    Döcke WD, Reinke P, Syrbe U, Platzer C, Asadullah K, Krausch D, Zuckermann H, Volk HD. Immunoparalysis in sepsis — from phenomenon to treatment strategies. Transplantationsmedizin 1997; 9: 55–65.Google Scholar
  9. 9.
    Woiciechowsky C, Asadullah K, Nestler D, Eberhardt B, Platzer C, Schöning B, Glöckner F, Lanksch WR, Volk HD, Döcke WD. Sympathetic activation triggers systemic IL-10 release in immunodepression induced by brain injury. Nature Med 1998; 4: 808–813.PubMedCrossRefGoogle Scholar
  10. 10.
    Randow F, Syrbe U, Meisel C, Krausch D, Zuckermann H, Platzer C, Volk HD. Mechanism of endotoxin desensitization — involvement of IL-10 and TGFß. J Exp Med 1995; 5: 1887–1892.CrossRefGoogle Scholar
  11. 11.
    Bone RC. Sir Isaac Newton, sepsis, SIRS, CARS. Crit Care Med 1996; 24:1125–1128.PubMedCrossRefGoogle Scholar
  12. 12.
    van Dissel J, van Langevelde P, Westendorp RG, Kwappenberg K, Frolich M. Anti-inflammatory cytokine profile and mortality in febrile patients. Lancet 1998; 351: 950–953.PubMedCrossRefGoogle Scholar
  13. 13.
    Asadullah K, Stephanek K, Leupold M, Jasulaitis D, Audring H, Volk HD, Sterry W, Döcke WD. IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach. J Clin Invest 1998; 101: 1–12.CrossRefGoogle Scholar
  14. 14.
    Wolk K, Döcke WD, v.Baehr V, Volk HD, Sabat R. Impaired antigen presentation by human monocytes during endotoxin tolerance. Blood 2000; in press.Google Scholar
  15. 15.
    Eskdale J, Gallagher G, Verweij CL, Keijsers V, Westendorp RG, Huizinga TW. Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci USA 1998; 95: 9465–9470.PubMedCrossRefGoogle Scholar
  16. 16.
    Randow F, Randow F, Döcke WD, Bundschuh DS, Hartung T, Wendel A, Volk HD. In vitro prevention and reversal of LPS desensitization by IFNg, IL-12, and GM-CSF. J Immunol 1997; 158:2911–2918.PubMedGoogle Scholar
  17. 17.
    Bundschuh D, Barsig J, Hartung T, Randow F, Döcke WD, Volk HD, Wendel A. GM-CSF and interferon-gamma restore the systemic TNFalpha response to endotoxin in lipopolysaccaride-desensitized mice. J Immunol 1997; 158: 2862–2871.PubMedGoogle Scholar
  18. 18.
    Reinke P. Plasmapheresis in the therapy of septic disease. Int J Artif Organs 1997; 19: 127–128.Google Scholar
  19. 19.
    Reinke P, Döcke WD, Kox W, Zuckermann H, Volk HD. New trends in immune monitoring of ICU patients. Dtsch Med Wschr 1999; 124: 1527–1530.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Hans-Dieter Volk
    • 1
  • Kerstin Wolk
    • 1
  • Robert Sabat
    • 1
  • Wolf-Dietrich Döcke
    • 1
  • Petra Reinke
    • 1
  1. 1.Institute of Medical Immunology and Department of Nephrology and Internal Intensive Medicine, CharitéHumboldt-University BerlinBerlinGermany

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