Effects of granulocyte colony-stimulating factor (G-CSF) treatment on granulocyte function and receptor expression in patients with ventilator-dependent pneumonia.
Considerable experimental evidence in animals suggests that treatment with G-CSF may have a beneficial effect in the management of severe infections in non-neutropenic hosts. This beneficial effect is attributed to an enhancement of granulopoiesis and neutrophil function, the latter possibly involving up-regulation of receptors on neutrophils that are involved in antibody-mediated cytotoxicity and killing of microorganisms. We compared neutrophil function and phenotype in blood and bronchoalveolar lavage fluid (BALF) of 10 patients with severe ventilator-dependent pneumonia, at baseline and following initiation of G-CSF treatment as adjunct to standard therapy. G-CSF treatment was associated with three-fold increased blood neutrophil counts at day 3 of treatment compared with baseline counts. Mean serum G-CSF concentration increased from 313 to 2007 pg/ml. After correction for lavage dilution effects, BALF G-CSF levels did not differ significantly from baseline, nor did neutrophil receptor expression (FcgammaRI, FcgammaRII, FcgammaRIII, CR3, and L-selectin) or indicators of neutrophil function such as respiratory burst activity, phagocytosis and killing of Candida albicans in BALF or blood. The mortality in this group of patients was 30% and compared favourably to the APACHE II-derived predicted mortality of 60%. We conclude that the possible therapeutic benefit of G-CSF administration in the early phase of severe bacterial pneumonia is not readily explained by its effect on baseline indicators of neutrophil function or receptor expression.
Hustinx
W N
WN
Department of Intensive Care & Clinical Toxicology, Utrecht University Hospital, The Netherlands.
Van Kessel
C P
CP
Heezius
E
E
Burgers
S
S
Lammers
J W
JW
Hoepelman
I M
IM
D000328:Adult; D000368:Aged; D001770:Blood Bactericidal Activity; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002176:Candida albicans; D002634:Chemotaxis, Leukocyte; D017714:Community-Acquired Infections / Q000628:therapy; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis; D011014:Pneumonia / Q000628:therapy*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis*; D011994:Recombinant Proteins; D016897:Respiratory Burst; D012122:Ventilators, Mechanical
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor