Skip to main content

Low Dose G-CSF to Augment Host Defense and Counteract Progression of Sepsis

  • Conference paper
Yearbook of Intensive Care and Emergency Medicine

Part of the book series: Yearbook of Intensive Care and Emergency Medicine ((YEARBOOK,volume 1996))

Abstract

Multiple trauma patients and patients undergoing major surgical operations are predisposed to life-threatening sepsis by an apparently acquired immunological deficiency, which is accompanied by a high mortality rate (40 to 60%) [1]. Neutrophils represent the first line of defense against invading bacteria. However, impaired neutrophil function has been reported in severely injured patients [2] and in patients during early septic shock [3]. Surgery resulted in further depression of neutrophil function in patients with intra-peritoneal infections [4]. In these patients, relapses of infections were associated with a diminution of neutrophil function prior to any clinical evidence for infection [4]. Thus, patients at risk of sepsis or with sepsis might benefit from prophylactic augmentation and restoration of neutrophil function. Unfortunately, until recently, there has been no choice to counteract granulocyte dysfunctions which have been described in posttraumatic patients [2]. However, in mice, recombinant human granulocyte colony-stimulating factor (rhG-CSF) improved survival in a well-established sepsis model [5]. G-CSF is one of the important hemopoietic factors which plays a central role in precursor cell proliferation and differentiation into neutrophils [6]. In addition to the stimulation of proliferation and maturation, G-CSF enhances a variety of functions of neutrophils, including chemotaxis [7], superoxide generation [8], bactericidal function [9] and phagocytic activity [9]. Moreover, G-CSF may have beneficial effects on feedback regulation of cytokines [5, 10]. Thus, G-CSF might activate neutrophils on the one hand and provide an anti-inflammatory effect on the other.

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 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
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. Casey LC, Balk RA, Bone RC (1993) Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med 119: 771–778

    PubMed  CAS  Google Scholar 

  2. Lanser ME, Mao P, Brown G, Coleman B, Siegel JH (1985) Serum-mediated depression of neutrophil chemiluminescence following blunt trauma. Ann Surg 202: 111–118

    Article  PubMed  CAS  Google Scholar 

  3. Vespa siano MC, Lewandoski JR, Zimmerman JJ (1993) Longitudinal analysis of neutrophil superoxide anion generation in patients with septic shock. Crit Care Med 21: 666–672

    Article  CAS  Google Scholar 

  4. Solomkin JS, Bauman MP, Nelson RD, Simmons RL (1981) Neutrophils dysfunction during the course of intra-abdominal infection. Ann Surg 194: 9–17

    Article  PubMed  CAS  Google Scholar 

  5. Gorgen I, Hartung T, Leist M, et al (1992) Granulocyte colony-stimulating factor treatment protects rodents against lipopolysaccharide-induced toxicity via suppression of systemic tumor necrosis factor-a. J Immunol 149: 919–924

    Google Scholar 

  6. Lieschke GJ, Burgess A W (1992) Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. N Engl J Med 327: 28–35

    Article  PubMed  CAS  Google Scholar 

  7. Wang JM, Chen ZG, Colella S, et al (1988) Chemotactic activity of recombinant human granulocyte colony-stimulating factor. Blood 72: 1456–1460

    PubMed  CAS  Google Scholar 

  8. Nathan CF (1989) Respiratory burst in adherent human neutrophils: Triggering by colony- stimulating factors CSF-GM and CSF-G. Blood 73: 301–306

    PubMed  CAS  Google Scholar 

  9. Roilides E, Walsh TJ, Pizzo PA, Rubin M (1991) Granulocyte colony-stimulating factor enhances the phagocytic and bactericidal activity of normal and defective human neutrophils. J Infect Dis 163: 579–583

    Article  PubMed  CAS  Google Scholar 

  10. Kanazawa M, Ishizaka A, Hasegawa N, Suzuki Y, Yokohama T (1992) Granulocyte colony-stimulating factor does not enhance endotoxin-induced acute lung injury in guinea pigs. Am Rev Respir Dis 145: 1030–1035

    Article  PubMed  CAS  Google Scholar 

  11. Sprikkelman A, de Wolf JTHM, Vellenga E (1994) The application of hematopoietic growth factors in drug-induced agranulocytosis: A review of 70 cases. Leukemia 8: 2031–2036

    PubMed  CAS  Google Scholar 

  12. Bone RC (1991) The pathogenesis of sepsis. Ann Intern Med 115: 457–469

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  14. Lynn WA, Golenbock DT (1992) Lipopolysaccharide antagonists. Immunol Today 13: 271–276

    Article  PubMed  CAS  Google Scholar 

  15. Keene AR, Cullen DJ (1983) Therapeutic intervention scoring system: Update 1983. Crit Care Med 11: 1–3

    Article  PubMed  CAS  Google Scholar 

  16. Bone RC (1992) American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20: 864–874

    Article  Google Scholar 

  17. Weiss M, Gross-Weege W, Harms B, Schneider EM (1996) Filgrastim (rhG-CSF) related modulation of the inflammatory response in patients at risk of sepsis or with sepsis. Cytokine (in press)

    Google Scholar 

  18. Schmitz S, Franke H, Brusis J, Wichmann HE (1993) Quantification of the cell kinetic effects of G-CSF using a model of human granulopoiesis. Exp Hematol 21: 755–760

    PubMed  CAS  Google Scholar 

  19. Lindemann A, Hermann F, Oster W, et al (1989) Hematologic effects of recombinant human granulocyte colony-stimulating factor in patients with malignancy. Blood 74: 2644–2651

    PubMed  CAS  Google Scholar 

  20. Weiss M, Gross-Weege W, Schneider M, et al (1995) Enhancement of neutrophil function by in vivo fllgrastim treatment for prophylaxis of sepsis in surgical intensive care patients. J Crit Care 10: 21–26

    Article  PubMed  CAS  Google Scholar 

  21. Selig C, Nothdurft W (1995) Cytokines and progenitor cells of granulocytopoiesis in peripheral blood of patients with bacterial infections. Infect Immun 63: 104–109

    PubMed  CAS  Google Scholar 

  22. Konig B, Konig W (1994) Effect of growth factors on Escherichia coli alpha-hemolysininduced mediator release from human inflammatory cells: Involvement of the signal transduction pathway. Infect Immun 62: 2085–2093

    PubMed  CAS  Google Scholar 

  23. Weiss M, Gross-Weege W, Wernet P, Neidhardt H, Harms B, Schneider M (1994) Filgrastim (rhG-CSF) for prophylaxis and therapy of sepsis in surgical intensive care patients: Neutrophil function. Clinical Intensive Care (Suppl) 5: 96 (Abst)

    Google Scholar 

  24. Simms HH, D’Amico R (1994) Polymorphonuclear leukocyte dysregulation during the systemic inflammatory response syndrome. Blood 83: 1398–1407

    PubMed  CAS  Google Scholar 

  25. Simms HH, D’Amico R (1994) Granulocyte colony-stimulating factor reverses septic shock-induced polymorphonuclear leukocyte dysfunction. Surgery 115: 85–93

    PubMed  CAS  Google Scholar 

  26. Repp R, Valerius T, Sendler A, et al (1991) Neutrophils express the high affinity receptor for IgG (FcgRI, CD64) after in vivo application of recombinant human granulocyte colony-stimulating factor. Blood 78: 885–889

    PubMed  CAS  Google Scholar 

  27. Kerst JM, de Haas M, van der Schoot E, et al (1993) Recombinant granulocyte colonystimulating factor administration to healthy volunteers: Induction of immunophenotypically and functionally altered neutrophils via an effect on myeloid progenitor cells. Blood 82: 3265–3272

    PubMed  CAS  Google Scholar 

  28. Erbe DV, Collins JE, Shen L, Graziano RF, Fanger MW (1990) The effect of cytokines on the expression and function of Fc receptors for IgG on human myeloid cells. Mol Immuno127: 57–67

    Google Scholar 

  29. De Haas M, Kerst JM, Van der Schoot CE, et al (1994) Granulocyte colony-stimulating factor administration to healthy volunteers analysis of the immediate activating effects on circulating neutrophils. Blood 84: 3885–3894

    PubMed  Google Scholar 

  30. Kuijpers TW, Tool ATJ, van der Schoot CE, et al (1991) Membrane surface antigen expression on neutrophils: A reappraisal of the use of surface markers for neutrophil activation. Blood 78: 1105–1111

    PubMed  CAS  Google Scholar 

  31. Clancy RM, Leszczynska-Piziak J, Abramson SB (1992) Nitric oxide, an endothelial cell relaxation factor, inhibitis neutrophil superoxide anion production via a direct action on the NADPH oxidase. J Clin Invest 90: 1116–1121

    Article  PubMed  CAS  Google Scholar 

  32. Springer TA (1990) Adhesion receptors of the immune system. Nature 346: 425–434

    Article  PubMed  CAS  Google Scholar 

  33. Hogg N (1992) Roll, roll, roll your leucocyte gently down the vein. Immunol Today 13: 113–115

    Article  PubMed  CAS  Google Scholar 

  34. Strieter RM, Kunkel SL (1994) Acute lung injury: The role of cytokines in the elicitation of neutrophils. J Invest Med 42: 643–649

    Google Scholar 

  35. Rao KM, Currie MS, Cohen HJ, Peters WP (1994) Alterations in L-selectin expression and elastase activity in neutrophils from patients receiving granulocyte colony-stimulating factor alone or in conjunction with high-dose chemotherapy with autologous bone marrow transplantation. Lymphokine Cytokine Res 13: 383–390

    PubMed  CAS  Google Scholar 

  36. Ohsaka A, Saionji K, Sato N, Mori T, Ishimoto K, Inamatsu T (1993) Granulocyte colony-stimulating factor downregulates the surface expression of the human leukocyte adhesion molecule-Ion human neutrophils in vitro and in vivo. Br J Haematol 84: 574–580

    Article  PubMed  CAS  Google Scholar 

  37. Tedder TF, Steeber DA, Pizcueta P (1995) L-selectin-deficient mice have impaired leukocyte recruitment into inflammatory sites. J Exp Med 181: 2259–2264

    Article  PubMed  CAS  Google Scholar 

  38. Cowley HC, Heney D, Gearing AJH, Hemingway I, Webster NR (1994) Increased circulating adhesion molecule concentrations in patients with the systemic inflammatory response syndrome: A prospective cohort study. Crit Care Med 22: 651–657

    Article  PubMed  CAS  Google Scholar 

  39. Sessler CN, Windsor AC, Schwartz M, et al (1995) Circulating ICAM-1 is increased in septic shock. Am J Respir Crit Care Med 151: 1420–1427

    PubMed  CAS  Google Scholar 

  40. Xu BH, Gonzalo JA, Pierre YS, et al (1994) Leukocytosis and resistance to septic shock in intercellular adhesion molecule I-deficient mice. J Exp Med 180: 95–109

    Article  PubMed  CAS  Google Scholar 

  41. Aoki Y, Hiromatsu K, Kobayashi N, et al (1995) Protective effect of granulocyte colonystimulating factor against T-cell-mediated lethal shock triggered by superantigens. Blood 86: 1420–1427

    PubMed  CAS  Google Scholar 

  42. Toumanen EI, Austrian R, Masure HR (1995) Pathogenesis of pneumococcal infection. N Engl J Med 11: 1280–1284

    Google Scholar 

  43. Kuhns DB, Alvord WG, Gallin JI (1995) Increased circulating cytokines, cytokine antagonists and E-selectin after intravenous administration of endotoxin in humans. J Infect Dis 171: 145–152

    Article  PubMed  CAS  Google Scholar 

  44. Hackett SP, Stevens DL (1992) Streptococcal toxic shock syndrome: Synthesis of tumor necrosis factor and interleukin-1 by monocytes stimulated with pyrogenic exotoxin A and streptolysin O. J Infect Dis 165: 879–885

    Article  PubMed  CAS  Google Scholar 

  45. Lorenz W, Reimund KP, Weitzel F, et al (1994) Granulocyte colony-stimulating factor prophylaxis before operation protects against lethal consequences of postoperative peritonitis. Surgery 116: 925–934

    PubMed  CAS  Google Scholar 

  46. Eichacker PQ, Waisman Y, Natanson C, et al (1994) Cardiopulmonary effects of granulocyte colony-stimulating factor in a canine model of bacterial sepsis. J Appl Physiol 77: 2366–2373

    PubMed  CAS  Google Scholar 

  47. Dinarello CA, Wolff SM (1993) The role of interleukin-1 in disease. N Engl J Med 328: 106–113

    Article  PubMed  CAS  Google Scholar 

  48. Hartung T, Docke WD, Gantner F, et al (1995) Effect of granulocyte colony-stimulating factor treatment on ex vivo blood cytokine response in human volunteers. Blood 85: 2482–2489

    PubMed  CAS  Google Scholar 

  49. van Zee KJ, DeForge LE, Fischer E, et al (1991) IL-8 in septic shock, endotoxemia, and after IL-1 administration. J Immunol 146: 3478–3482

    PubMed  Google Scholar 

  50. Kilgore KS, Shen JP, Miller BF, Ward PA, Warren JS (1995) Enhancement by the complement membrane attack complex of tumor necrosis factor-α induced endothelial cell expression of E-selectin and ICAM-1. J Immunol 155: 1434–1441

    PubMed  CAS  Google Scholar 

  51. Denzlinger C, Holler E, Reisbach G, Hiller E, Wilmanns W (1994) Granulocyte colonystimulating factor inhibits the endogenous leukotriene production in tumour patients. Br J Haematol 86: 881–882

    Article  PubMed  CAS  Google Scholar 

  52. Emminger W, Emminger-Schmidmeier W, Peters C, et al (1990) Capillary leak syndrome during low dose granulocyte-macrophage colony-stimulating factor (rh GMCSF) treatment of a patient in a continuous febrile state. Blut 61: 219–221

    Article  PubMed  CAS  Google Scholar 

  53. Izumi T, Muroi K, Takatoku MA, Imagawa S, Hatake K, Miura Y (1994) Development of acute myeloblastic leukaemia in a case of aplastic anaemia treated with granulocyte colony-stimulating factor. Br J Haematol 87: 666–668

    Article  PubMed  CAS  Google Scholar 

  54. Kojima S, Inaba J, Kondo M, Kato K, Matsuyama T, Kodera Y (1995) Development of myelodysplasia with monosomy 7 in children with severe aplastic anemia after treatment with recombinant granulocyte colony-stimulating factor. Exp Hematol 230: 901–906

    Google Scholar 

  55. Schilero GJ, Oropello J, Benjamin E (1995) Impairment in gas exchange after granulocyte colony-stimulating factor (G-CSF) in a patient with the adult respiratory distress syndrome. Chest 107: 276–278

    Article  PubMed  CAS  Google Scholar 

  56. Demuynck H, Zachee P, Verhoef GEG, et al (1995) Risk of rhG-CSF treatment in druginduced agranulocytosis. Ann Hematol 70: 143–147

    Article  PubMed  CAS  Google Scholar 

  57. Heyll A, Aul C, Gogolin F, Thomas M, et al (1991) Granulocyte colony-stimulating factor (G-CSF) treatment in a neutropenic leukemia patient with diffuse interstitial pulmonary infiltrates. Ann Hematol 63: 328–332

    Article  PubMed  CAS  Google Scholar 

  58. Gillis S (1991) Cytokine receptors. Curr Opin Immunol 3: 315–319

    Article  PubMed  CAS  Google Scholar 

  59. Tweardy DJ, Burkhardt AL, Bolen J, Geahlen RL, Corey SJ (1993) G-CSF receptor signaling involves SRC-related and non-SRC-related tyrosine kinases with evidence of a threecomponent complex. In: Abraham NG, Shadduck RK, Levine AS, Takaku F (eds) Molecular Biology of Haematopoiesis. Vol 3. Intercept, Andover, pp 607–619

    Google Scholar 

  60. Tian SS, Lamb P, Seidel HM, Stein RB, Rosen J (1994) Rapid activation of the STAT3 transcription factor by granulocyte colony-stimulating factor. Blood 84: 1760–1764

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Weiss, M., Schneider, E.M., Radermacher, P. (1996). Low Dose G-CSF to Augment Host Defense and Counteract Progression of Sepsis. In: Vincent, JL. (eds) Yearbook of Intensive Care and Emergency Medicine. Yearbook of Intensive Care and Emergency Medicine, vol 1996. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80053-5_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-80053-5_14

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-60552-2

  • Online ISBN: 978-3-642-80053-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics