Administration of rHuGM-CSF activates monocyte reactive oxygen species secretion and adhesion molecule expression in vivo in patients following high-dose chemotherapy

Br J Haematol. 1995 May;90(1):31-40. doi: 10.1111/j.1365-2141.1995.tb03377.x.


Microbicidal and cytocidal products of the respiratory burst and integrin adhesion molecule expression have been studied in monocytes from patients who received rHuGM-CSF during regeneration after high-dose chemotherapy. In this study, administration of rHuGM-CSF after high-dose chemotherapy significantly augmented the secretion of inducible products of the monocyte respiratory burst. Monocyte activation persisted for several weeks after the cessation of GM-CSF therapy. Under in vitro conditions that mimicked gram-negative (LPS) and gram-positive (opsonized Staphylococcus aureus) sepsis, the monocyte responded to such stimulation by exhibiting an enhanced release of hydrogen peroxide at both regeneration and several weeks later (P < 0.001). Similarly, GM-CSF administration significantly augmented the phenotypic expression of the beta 2-integrin adhesion molecules and allowed the leucocyte-specific selectin, LAM-1, and the beta 2-integrins to respond normally to inflammatory stimulation by LPS. We further present evidence that GM-CSF therapy restored the otherwise refractory status of monocytes to inflammatory stimulation that existed in those patients given chemotherapy alone. The restoration of monocyte responsiveness by GM-CSF following high-dose chemotherapy could be a potentially valuable and hitherto not described action of rHuGM-CSF on monocyte function. We conclude that administration of GM-CSF may have the potential for restoring as well as augmenting the anti-microbial and anti-tumour function of the monocyte after high-dose chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / pharmacology
  • CD18 Antigens
  • Cell Adhesion Molecules / blood*
  • Cyclophosphamide / therapeutic use*
  • Escherichia coli
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Integrins / analysis
  • L-Selectin
  • Lipopolysaccharides / pharmacology
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology*
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Reactive Oxygen Species / metabolism*
  • Recombinant Proteins / pharmacology
  • Respiratory Burst / drug effects
  • Staphylococcus aureus / immunology
  • Tetradecanoylphorbol Acetate / pharmacology


  • Antigens, Bacterial
  • CD18 Antigens
  • Cell Adhesion Molecules
  • Integrins
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • Recombinant Proteins
  • L-Selectin
  • N-Formylmethionine Leucyl-Phenylalanine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Cyclophosphamide
  • Tetradecanoylphorbol Acetate