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Bactericidal activity response of blood neutrophils from critically ill patients to in vitro granulocyte colony-stimulating factor stimulation

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Abstract

Objective

Neutrophil function impairment is common in nonneutropenic critically ill patients. Whether granulocyte colony-stimulating factor (G-CSF) may be useful for preventing nosocomial infection in these patients is debated. The response of blood neutrophils from critically ill patients to G-CSF was investigated in vitro.

Design and setting

Prospective study, laboratory investigation in two intensive care units.

Patients

52 critically ill patients without immunosuppression.

Measurements

Neutrophils obtained from 52 patients on the 5th day of their intensive care unit stay were incubated with and without G-CSF (1, 10, 100 ng/ml). Reactive oxygen species (ROS) release and bactericidal activity against Staphylococcus aureus and Pseudomonas aeruginosa were evaluated. Plasma cytokines (interleukin 10, tumor necrosis factor α, and G-CSF) were measured.

Results

Median values (25th–75th percentiles) indicated no stimulatory effect of G-CSF on neutrophil bactericidal activity against either organism: S. aureus, 100% (95–109) of the unstimulated condition with 1 ng/ml G-CSF, and P. aeruginosa , 102% (98–109) with 1 ng/ml G-CSF. However, wide interindividual variability was found, ranging from marked inhibition to marked stimulation. Similar variability was found for ROS release. No correlations were found between ROS release and bactericidal activities against either bacterial strain. Inhibition of neutrophil bactericidal activity by G-CSF was associated with significantly higher plasma interleukin 10 concentrations. Plasma G-CSF levels were significantly higher in patients whose neutrophil bactericidal activity was unresponsive to G-CSF, suggesting G-CSF receptor downregulation.

Conclusions

The effect of G-CSF on in vitro neutrophil bactericidal activity varied widely, depending on endogenous levels of G-CSF and was not predictable based on severity scores.

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Authors and Affiliations

  1. Unité INSERM U 492, Faculté de Médecine, Université Paris XII, 8 rue du Général Sarrail, 94010, Créteil, France

    Kun Yang, Élie Azoulay, Lynda Attalah, Laurent Brochard, Alain Harf & Christophe Delclaux

  2. Medical Intensive Care Unit, Henri Mondor Hospital, AP-HP, Créteil, France

    Jean-Ralph Zahar, Laurent Brochard & Christian Brun-Buisson

  3. Surgical Intensive Care Unit, Henri Mondor Hospital, AP-HP, Créteil, France

    Andry Van de Louw, Charles Cerf & Philippe Duvaldestin

  4. Laboratory of Bacteriology, Henri Mondor Hospital, AP-HP, Créteil, France

    Claude-James Soussy

  5. Department of Physiology, Henri Mondor Hospital, AP-HP, Créteil, France

    Alain Harf & Christophe Delclaux

Authors
  1. Kun Yang
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  2. Élie Azoulay
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  3. Lynda Attalah
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  4. Jean-Ralph Zahar
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  6. Charles Cerf
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  7. Claude-James Soussy
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  9. Laurent Brochard
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  10. Christian Brun-Buisson
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  11. Alain Harf
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  12. Christophe Delclaux
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Corresponding author

Correspondence to Christophe Delclaux.

Additional information

This study was supported by a grant from Aventis France

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Yang, K., Azoulay, É., Attalah, L. et al. Bactericidal activity response of blood neutrophils from critically ill patients to in vitro granulocyte colony-stimulating factor stimulation. Intensive Care Med 29, 396–402 (2003). https://doi.org/10.1007/s00134-002-1623-9

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  • DOI: https://doi.org/10.1007/s00134-002-1623-9

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