Skip to main content

Cytokine Neutralization: An Overview

  • Chapter
Immune Response in the Critically Ill

Part of the book series: Update in Intensive Care Medicine ((UICMSOFT,volume 31))

Abstract

An excessive inflammatory response accompanies the initial stages of severe infection and appears to contribute to organ system failure and death in this setting [13]. A number of immunomodulatory therapies aimed at decreasing the dysregulated inflammatory response have been examined in patients with sepsis (Table 1). Despite initially encouraging results with many of these approaches in Phase II clinical trials, larger Phase III studies have not demonstrated benefit. In contrast to the lack of effect of immunomodulatory agents in sepsis, therapies directed against specific pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α or interleukin (IL)-1,have produced remarkable clinical response in diseases such as rheumatoid arthritis and Crohn’s disease [46].

Some immunomodulatory therapies examined in sepsis

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abraham E (1997) Therapies for sepsis. Emerging therapies for sepsis and septic shock. West J Med 166:195–200

    PubMed  CAS  Google Scholar 

  2. Parrillo JE, Parker MM, Natanson C, et al (1990) Septic shock in humans. Ann Intern Med 113:227–242

    PubMed  CAS  Google Scholar 

  3. Zeni F, Freeman B, Natanson C (1997) Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med 25:1095–1100

    Article  PubMed  CAS  Google Scholar 

  4. Targan SR, Hanauer SB, van Deventer S J, et al (1997) A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. New Engl J Med 337:1029–1035

    Article  PubMed  CAS  Google Scholar 

  5. Lorenz HM, Antoni C, Valerius T, et al (1996) In vivo blockade of TNF-alpha by intravenous infusion of a chimeric monoclonal TNF-alpha antibody in patients with rheumatoid arthritis. Short term cellular and molecular effects. J Immunol 156:1646–1653

    PubMed  CAS  Google Scholar 

  6. Elliott MJ, Maini RN, Feldmann M, et al (1994) Repeated therapy with monoclonal antibody to tumor necrosis factor alpha (cA2) in patients with rheumatoid arthritis. Lancet 344:1125–1127

    Article  PubMed  CAS  Google Scholar 

  7. Bone RC, Balk RA, Cerra FB, et al (1992) ACCP/SCCM consensus conference: Definitions for sepsis and organ failure and guidehnes for the use of innovative therapies in sepsis. Chest 101:1644–1655

    Article  PubMed  CAS  Google Scholar 

  8. Bone RC, Fisher Jr. CJ, Clemmer TP, et al (1989) Sepsis syndrome: A valid clinical entity Crit Care Med 17:389–393

    Article  PubMed  CAS  Google Scholar 

  9. Abraham E, Wunderink R, Silverman H, et al (1995) Monoclonal antibody to human tumor necrosis factor alpha (TNF MAb): Efficacy and safety in patients with the sepsis syndrome. JAMA 273:934–941

    Article  PubMed  CAS  Google Scholar 

  10. Cohen J, Carlet J (1996) INTERSEPT: An international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-α in patients with sepsis. Crit Care Med 24:1431–1440

    Article  PubMed  CAS  Google Scholar 

  11. Abraham E, Glauser MP, Butler T, et al (1997) p55 tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock. JAMA 277:1531–1534

    Article  PubMed  CAS  Google Scholar 

  12. Opal SM, Fisher CJ, Pribble JP, et al (1997) The confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III randomized, double-blind, placebo-controlled, multicenter trial. Crit Care Med 25:1115–1124

    Article  PubMed  CAS  Google Scholar 

  13. Abraham E, Anzueto A, Gutierrez G, et al (1998) Monoclonal antibody to human tumor necrosis factor alpha (TNF Mab) in the treatment of patients with septic shock: A multi-center, placebo controlled, randomized, double-blind clinical trial. Lancet 351:929–933

    PubMed  CAS  Google Scholar 

  14. Zanetti G, Heumann D, Gerain J, et al (1992) Cytokine production after intravenous or peritoneal gram-negative bacterial challenge in mice. J Immunol 148:1890–1897

    PubMed  CAS  Google Scholar 

  15. Fisher CJ Jr., Agosti JM, Opal SM, et al (1996) Treatment of septic shock with the tumor necrosis factor receptor Fc fusion protein. N Engl J Med 334:1697–1702

    Article  PubMed  CAS  Google Scholar 

  16. Sprung CL, Finch RG, Thijs LG, Glauser MP (1996) International sepsis trial (INTERSEPT): role and impact of a clinical evaluation committee. Crit Care Med 24:1441–1447

    Article  PubMed  CAS  Google Scholar 

  17. Ohlsson K, Bjork P, Bergenfeldt M, Hageman R, Thompson RC (1990) Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature 348:550–552

    Article  PubMed  CAS  Google Scholar 

  18. Wakabayashi G, Gelfand JA, Burke JF, Thompson RC, Dinarello CA (1991) A specific receptor antagonist for interleukin-1 prevents Escherichia coli-induced shock. FASEB J 5:338–343

    PubMed  CAS  Google Scholar 

  19. Hawes AS, Fischer E, Marano MA, et al (1993) Comparison of peripheral blood leukocyte kinetics after live Escherichia coli, endotoxin, or interleukin-1 alpha administration. Studies using a novel interleukin-1 receptor antagonist. Ann Surg 218:79–90

    Article  PubMed  CAS  Google Scholar 

  20. Fischer E, Marano MA, Van Zee KJ, et al (1992) Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia. J Clin Invest 89:1551–1557

    Article  PubMed  CAS  Google Scholar 

  21. Fisher CJ Jr., Slotman GJ, Opal SM, et al (1994) Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial. The IL-1RA Sepsis Syndrome Study Group. Crit Care Med 22:12–21

    PubMed  Google Scholar 

  22. Fisher CJ Jr, Dhainaut JF, Opal SM, et al (1994) Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-bUnd, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA 271:1836–1843

    Article  PubMed  Google Scholar 

  23. Tracey KJ, Fong Y, Hesse DG, et al (1987) Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteremia. Nature 330:662–664

    Article  PubMed  CAS  Google Scholar 

  24. Fong Y, Tracey KJ, Moldawer LL, et al (1989) Antibodies to cachectin/TNF reduce interleukin-1 and interleukin-6 appearance during lethal bacteremia. J Exp Med 170:1627–1633

    Article  PubMed  CAS  Google Scholar 

  25. Hinshaw LB, Tekamp-Olson P, Chang AC, et al (1990) Survival of primates in LDioo septic shock following therapy with antibody to tumor necrosis factor (TNF). Cire Shock 30:279–292

    CAS  Google Scholar 

  26. Van Zee KJ, Moldawer LL, Oldenburg HAS, et al (1996) Protection against lethal Escherichia coli bacteremia in baboons (Papio anubis) by pretreatment with a 55-kDa TNF receptor (CD120a)-Ig fusion protein, Ro 45-2081. J Immunol 156:2221–2230

    PubMed  Google Scholar 

  27. Hinshaw LB, Emerson TE Jr., Taylor FB Jr., et al (1992) Lethal S. aureus shock in primates: prevention of death with anti-TNF antibody J Trauma 33:568–573

    Article  PubMed  CAS  Google Scholar 

  28. Vincent JL, Bakker J, Marecaux G, Schandene L, Kahn RJ, Dupont E ( 1992) Administration of anti-TNF antibody improves left ventricular function in septic shock patients. Results of a pilot study Chest 101:810–815

    Article  PubMed  CAS  Google Scholar 

  29. Dhainaut JF, Vincent JL, Richard C, et al (1995) CDP571, a humanized antibody to human tumor necrosis factor-α: Safety, pharmacokinetics, immune response, and influence of the antibody on cytokine concentrations in patients with septic shock. Crit Care Med 23:1461–1469

    Article  PubMed  CAS  Google Scholar 

  30. Reinhart K, Wiegand-Lohnert C, Grimminger F, et al (1996) Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK 195F, in patients with sepsis and septic shock: A multicenter, randomized, placebo-controlled, dose-ranging study Crit Care Med 24:733–742

    Article  PubMed  CAS  Google Scholar 

  31. Giroir BP, Quint PA, Barton P, et al (1997) Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsis. Lancet 350:1439–1443

    Article  PubMed  CAS  Google Scholar 

  32. Bone RC (1994) Gram-positive organisms and sepsis. Arch Intern Med 154:26–34

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Abraham, E. (2002). Cytokine Neutralization: An Overview. In: Marshall, J.C., Cohen, J. (eds) Immune Response in the Critically Ill. Update in Intensive Care Medicine, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57210-4_25

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-57210-4_25

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-42589-2

  • Online ISBN: 978-3-642-57210-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics