In vivo induction of functional Fc gammaRI (CD64) on neutrophils and modulation of blood cytokine mRNA levels in cancer patients treated with G-CSF (rMetHuG-CSF).
Neutrophils from 13 children who received G-CSF for the collection of peripheral blood progenitors while they were in haematological steady state were studied at various times after G-CSF injection for Fc gammaR expression (Fc gammaRI or CD64, Fc gammaRII or CD32, and Fc gammaRIII or CD16) and for their ability to exert antibody-dependent cell cytotoxicity (ADCC) through Fc gammaRI. Changes in IFNgamma, IL8, IL10, MCP1 and TNF alpha mRNA levels in peripheral blood cells were also studied 4 h and 24 h after the first G-CSF injection. Fc gammaRI expression increased strongly after 24 h and then remained at the same level throughout treatment. In contrast, Fc gammaRIII expression sharply decreased at day 1 and diminished even further thereafter. No change in Fc gammaRII was observed. ADCC exerted by neutrophils through Fc gammaRI started to increase after 24 h with the peak level at day 5. Cytokine mRNA analyses indicated a reproducible and strong increase of IL8 mRNA (11/13 children) after 24 h, whereas the changes in the mRNA levels of the other cytokines tested were more heterogenous (TFNgamma: three; IL10: six; MCP1: five: TNF alpha: four, of the 13 children). Therefore this study opens the way to an optimized therapeutic schedule for the combined use of G-CSF and monoclonal antibodies in adjuvant immuno-intervention.
Michon
J M
JM
INSERM Unité 255, Institut Curie, Paris, France.
Gey
A
A
Moutel
S
S
Tartour
E
E
Meresse
V
V
Fridman
W
W
Teillaud
J L
JL
D000293:Adolescent; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000494:pharmacology; D007958:Leukocyte Count; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology*; D011994:Recombinant Proteins; D015854:Up-Regulation
D016207:Cytokines; D016209:Interleukin-8; D012333:RNA, Messenger; D017452:Receptors, IgG; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim