Skip to main content
SpringerLink
Log in

Pro-Inflammatory Cytokines: Double-Edged Swords in the Pathogenesis of Bacterial Infection

  • Chapter
Mechanisms of Organ Dysfunction in Critical Illness

Part of the book series: Update in Intensive Care and Emergency Medicine ((UICMSOFT,volume 38))

  • 107 Accesses

Abstract

Cytokines are small proteins that orchestrate a variety of inflammatory reactions. Many different cell types are able to produce cytokines upon stimulation with bacterial, and other, stimuli. As a consequence, the concentrations of cytokines increase substantially during infection, especially at sites of bacterial multiplication. In this chapter, recent insights into the seemingly paradoxical role of pro-inflammatory cytokines, beneficial for antibacterial defense mechanisms on the one hand, and potentially toxic to the host on the other hand, are discussed.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover 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. Van der Poll T, van Deventer SJH (1999) Cytokines and anticytokines in the pathogenesis of sepsis. Infect Dis Clin North Am 13:413–426

    Article  PubMed  Google Scholar 

  2. Bazzoni F, Beutler B (1996) The tumor necrosis factor ligand and receptor families. N Engl J Med 334:1717–1725

    Article  PubMed  CAS  Google Scholar 

  3. Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87:2095–2147

    PubMed  CAS  Google Scholar 

  4. Okusawa S, Gelfland JA, Ikejima T, Connolly RJ, Dinarello CA (1988) Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition. J Clin Invest 81:1162–1172

    Article  PubMed  CAS  Google Scholar 

  5. Tracey KJ, Beutler B, Lowry SF, et al (1986) Shock and tissue injury induced by recombinant human cachectin. Science 234:470–474

    Article  PubMed  CAS  Google Scholar 

  6. Van der Poll T, Biiller HR, ten Cate H, et al (1990) Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 322:1622–1627

    Article  PubMed  Google Scholar 

  7. Van der Poll T, van Deventer SJH, Hack CE, et al (1992) Effects on leukocytes following injection of tumor necrosis factor into healthy humans. Blood 79:693–698

    PubMed  Google Scholar 

  8. Ogilvie AC, Hack CE, Wagstaff J, et al (1996) IL-lβ does not cause neutrophil degranulation but does lead to IL-6, IL-8, and nitrite/nitrate release when used in patients with cancer. J Immunol 156:389–394

    PubMed  CAS  Google Scholar 

  9. Aderka D, Le J, Vilcek J (1989) IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells and in mice. J Immunol 143: 3517–3523

    PubMed  CAS  Google Scholar 

  10. Tilg H, Trehu E, Atkins MB, Dinarello CA, Mier JW (1994) Interleukin-6 (IL-6) as an antiinflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood 83:113–118

    PubMed  CAS  Google Scholar 

  11. Stouthard JML, Levi M, Hack CE, et al (1996) Interleukin 6 stimulates coagulation, not fibrinolysis, in humans. Thromb Haemostas 76:738–742

    CAS  Google Scholar 

  12. Preiser JC, Schmartz D, van der Linden P, et al (1991) Interleukin-6 administration has no acute hemodynamic or hematologic effect in the dog. Cytokine 3:1–4

    Article  PubMed  CAS  Google Scholar 

  13. Boehm U, Klamp T, Groot M, Howard JC (1997) Cellular responses to interferon-y. Annu Rev Immunol 15:749–795

    Article  PubMed  CAS  Google Scholar 

  14. Romani L, Pucetti P, Bistoni F (1997) Interleukin-12 in infectious diseases. Clin Microbiol Rev 10:611–636

    PubMed  CAS  Google Scholar 

  15. Dinarello CA (2000) Interleukin-18, a proinflammatory cytokine. Eur Cytokine Netw 11: 483–486

    PubMed  CAS  Google Scholar 

  16. Lauw FN, Dekkers PEP, te Velde AA, et al (1999) Interleukin 12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees. J Infect Dis 179:646–652

    Article  PubMed  CAS  Google Scholar 

  17. Opal SM, Wherry JC, Grint P (1998) Interleukin-10: potential benefits and possible risks in clinical infectious diseases. Clin Infect Dis 27:1497–1507

    Article  PubMed  CAS  Google Scholar 

  18. De Vries JE (1996) Molecular and biological characteristics of interleukin-13. Chem Immunol 63:204–218

    Article  PubMed  Google Scholar 

  19. Bone RC, Grodzin CJ, Balk RA (1997) Sepsis: a new hypothesis for pathogenesis of the disease process. Chest 112:235–243

    Article  PubMed  CAS  Google Scholar 

  20. Munoz C, Carlet J, Fitting C, Misset B, Blériot JP, Cavaillon JM (1991) Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest 88:1747–1754

    Article  PubMed  CAS  Google Scholar 

  21. Van Deuren M, Van der Ven-Jongekrijg J, Demacker PNM, et al (1994) Differential expression of proinflammatory cytokines and their inhibitors during the course of meningococcal infections. J Infect Dis 169:157–161

    Article  PubMed  Google Scholar 

  22. Van der Poll T, Coyle SM, Barbosa K, Braxton CC, Lowry SF (1996) Epinephrine inhibits tumor necrosis factor and potentiates interleukin 10 release during human endotoxemia. J Clin Invest 97:713–719

    Article  PubMed  Google Scholar 

  23. Van der Poll T, Barber AE, Coyle SM, Lowry SF (1996) Hypercortisolemia increases plasma interleukin 10 concentrations during human endotoxemia. J Clin Endocrin Metab 81: 3604–3606

    Article  Google Scholar 

  24. Lowry SF, Calvano SE, van der Poll T (1995) Measurement of inflammatory mediators in clinical sepsis. In: Sibbald WJ, Vincent JL (eds) Clinical Trials for the Treatment of Sepsis. Springer-Verlag, Heidelberg, pp:86–105

    Chapter  Google Scholar 

  25. Lauw FN, Simpson AJH, Prins JM., et al (1999) Elevated plasma concentrations of interferon-γ (IFN-γ) and the IFN-γ-inducing cytokines interleukin-18 (IL-18), IL-12 and IL-15 in severe melioidosis. J Infect Dis 180:1878–1885

    Article  PubMed  CAS  Google Scholar 

  26. Van der Poll T, van Deventer SJH (1999) Endotoxemia in healthy subjects as a human model of inflammation. In: Cohen J, Marshall J (eds) The Immune Response in the Critically 111. Springer-Verlag, Heidelberg, pp:335–357

    Google Scholar 

  27. Dehoux MS, Boutten A, Ostinelli J, et al (1994) Compartimentalized cytokine production within the human lung in unilateral pneumonia. Am J Respir Crit Care Med 150:710–716

    Article  PubMed  CAS  Google Scholar 

  28. Standiford TJ, Tsai WC, Mehard B, Moore TA (2000) Cytokines as targets of immunotherapy in bacterial pneumonia. J Lab Clin Med 135:129–138

    Article  PubMed  CAS  Google Scholar 

  29. Beutler B, Milsark IW, Cerami A (1985) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229:869–871

    Article  PubMed  CAS  Google Scholar 

  30. Pfeffer K, Matsuyama T, Kündig TM, et al (1993) Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 73:457–467

    Article  PubMed  CAS  Google Scholar 

  31. Van Zee KJ, Stackpole SA, Montegut WJ, et al (1994) A human tumor necrosis factor (TNF) <x mutant that binds exclusively to the p55 TNF receptor produces toxicity in the baboon. J Exp Med 179:1185–1191

    Article  PubMed  Google Scholar 

  32. Ohlsson K, Bjórk 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 

  33. 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 

  34. Fantuzzi G, Zheng H, Faggioni R, et al (1996) Effect of endotoxin in IL-lB-deficient mice. J Immunol 157:291–296

    PubMed  CAS  Google Scholar 

  35. Glaccum MB, Stocking KL, Charrier K, et al (1997) Phenotypic and functional characterization of mice that lack the type I receptor for IL-1. J Immunol 159:3364–3371

    PubMed  CAS  Google Scholar 

  36. Acton RD, Dahlberg PS, Uknis ME, et al (1996) Differential sensitivity to Escherichia coli infection in mice lacking tumor necrosis factor p55 or interleukin-1 p80 receptors. Arch Surg 131:1216–1221

    Article  PubMed  CAS  Google Scholar 

  37. Dalrymple SA, Slattery R, Aud DM, Krishna M, Lucian LA, Murray R (1996) Interleukin-6 is required for a protective immune response to systemic Escherichia coli infection. Infect Immun 64:3231–3235

    PubMed  CAS  Google Scholar 

  38. Van der Poll T, Levi M, Hack CE, et al (1994) Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. J Exp Med 179:1253–1259

    Article  PubMed  Google Scholar 

  39. Netea MG, Fantuzzi G, Kullberg B, et al (2000) Neutralization of IL-18 reduces neutrophil tissue accumulation and protects mice against lethal Escherichia coli and Salmonella typhimurium endotoxemia. J Immunol 164:2644–2649

    PubMed  CAS  Google Scholar 

  40. Wysocka M, Kubin M, Vieira LQ, et al (1995) Interleukin-12 is required for interferon-γ production and lethality in lipopolysaccharide-induced shock in mice. Eur J Immunol 25:672–676

    Article  PubMed  CAS  Google Scholar 

  41. Silva AT, Cohen J (1992) Role of interferon-γ in experimental gram-negative sepsis. J Infect Dis 166:331–335

    Article  PubMed  CAS  Google Scholar 

  42. Car BD, Eng VM, Schnyder B, et al (1994) Interferon y receptor deficient mice are resistant to endotoxic shock. J Exp Med 179:1437–1444

    Article  PubMed  CAS  Google Scholar 

  43. Gérard C, Bruyns C, Marchant A, et al (1993) Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. J Exp Med 177:547–550

    Article  PubMed  Google Scholar 

  44. Van der Poll T, Jansen PM, Montegut WJ, et al (1997) Effects of IL-10 on systemic inflammatory responses during sublethal primate endotoxemia. J Immunol 158:1971–1975

    PubMed  Google Scholar 

  45. Pajkrt D, Camoglio L, Tiel-van Buul MCM, et al (1997) Attenuation of proinflammatory response by recombinant human IL-10 in human endotoxemia; the effect of timing of rhIL-10 administration. J Immunol 158:3971–3977

    PubMed  CAS  Google Scholar 

  46. Muchamuel T, Menon S, Pisacane P, Howard MC, Cockayne DA (1997) IL-13 protects mice from lipopolysaccharide-induced lethal endotoxemia: correlation with down-modulation of TNF-α, IFN-γ, and IL-12 production. J Immunol 158:2898–2903

    PubMed  CAS  Google Scholar 

  47. Pajkrt D, van der Poll T, Levi M, et al (1997) Interleukin 10 inhibits activation of coagulation and fibrinolysis during human endotoxemia. Blood 89:2701–2705

    PubMed  CAS  Google Scholar 

  48. Marchant A, Bruyns C, Vandenabeele P, et al (1994) IL-10 controls IFN-γ and TNF production during experimental endotoxemia. Eur J Immunol 24:1167–1171

    Article  PubMed  CAS  Google Scholar 

  49. Berg DJ, Kühn R, Rajewsky K, et al (1995) Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Shwartzman reaction but not endotoxin tolerance. J Clin Invest 96:2339–2347

    Article  PubMed  CAS  Google Scholar 

  50. Greenberger MJ, Kunkel SL, Strieter RM et al (1996) IL-12 gene therapy protects mice in lethal Klebsiella pneumonia. J Immunol 157:3006–3012

    PubMed  CAS  Google Scholar 

  51. Van der Poll T, Keogh CV, Buurman WA, Lowry SF (1997) Passive immunization against Tumor necrosis factor alpha impairs host defense during pneumococcal pneumonia. Am J Respir Crit Care Med 155:603–608

    Article  PubMed  Google Scholar 

  52. Van der Poll T, Keogh CV, Guirao X, Buurman WA, Kopf M, Lowry SF (1997) Interleukin-6 gene deficient mice show impaired defense against streptococcal pneumonia. J Infect Dis 176:439–444

    Article  PubMed  Google Scholar 

  53. Greenberger MJ, Strieter RM, Kunkel SL, Danforth JM, Goodman RE, Standiford TJ (1995) Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia. J Immunol 155:722–729

    PubMed  CAS  Google Scholar 

  54. van der Poll T, Marchant A, Keogh CV, Goldman M, Lowry SF (1996) Interleukin-10 impairs host defense in murine pneumococcal pneumonia. J Infect Dis 174:994–1000

    Article  PubMed  Google Scholar 

  55. Echtenacher B, Falk W, Mannel DN, Krammer PH (1990) Requirement of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis. J Immunol 145: 3762–3766

    PubMed  CAS  Google Scholar 

  56. Sewnath ME, Olszyna DP, Birjmohun RS, ten Kate FJW, Gouma DJ, van der Poll T (2001) Interleukin 10 deficient mice demonstrate multiple organ failure and increased mortality during Escherichia coli peritonitis despite an accelerated bacterial clearance. J Immunol 166:6323–6331

    PubMed  CAS  Google Scholar 

  57. Matsukawa A, Hogaboam CM, Lukacs NW, et al (2000) Expression and contribution of endogenous IL-13 in an experimental model of sepsis. J Immunol 164:2738–2744

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Academic Medical Center, Room G2-130 Meibergdreef 9, 1105, AZ Amsterdam, The Netherlands

    T. van der Poll

Authors
  1. T. van der Poll
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Intensive Care Unit, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK

    Timothy W. Evans

  2. Division of Critical Care Medicine, University of Pittsburgh Medical Center, Scaife Hall, Room 606, 3550 Terrace Street, Pittsburgh, PA, 15264, USA

    Mitchell P. Fink

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

van der Poll, T. (2002). Pro-Inflammatory Cytokines: Double-Edged Swords in the Pathogenesis of Bacterial Infection. In: Evans, T.W., Fink, M.P. (eds) Mechanisms of Organ Dysfunction in Critical Illness. Update in Intensive Care and Emergency Medicine, vol 38. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56107-8_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-56107-8_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-42692-9

  • Online ISBN: 978-3-642-56107-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation