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


METHODS
Prospective study, laboratory investigation in two intensive care units.


METHODS
52 critically ill patients without immunosuppression.


METHODS
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 alpha, 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.
Yang
Kun
K
Unité INSERM U 492, Faculté de Médecine, Université Paris XII, 8 rue du Général Sarrail, 94010 Créteil, France.
Azoulay
Elie
E
Attalah
Lynda
L
Zahar
Jean-Ralph
JR
Van de Louw
Andry
A
Cerf
Charles
C
Soussy
Claude-James
CJ
Duvaldestin
Philippe
P
Brochard
Laurent
L
Brun-Buisson
Christian
C
Harf
Alain
A
Delclaux
Christophe
C
D000328:Adult; D001770:Blood Bactericidal Activity / Q000502:physiology*; D016009:Chi-Square Distribution; D016638:Critical Illness; D016207:Cytokines / Q000097:blood; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D011446:Prospective Studies; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000097:blood; D013211:Staphylococcus aureus / Q000276:immunology*; D018709:Statistics, Nonparametric
D016207:Cytokines; D017382:Reactive Oxygen Species; D016179:Granulocyte Colony-Stimulating Factor