Close association between clearance of recombinant human granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor on neutrophils in cancer patients.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is used to counter chemotherapy-induced neutropenia. Our previous study showed an inverse correlation between serum rhG-CSF levels and the number of circulating neutrophils in cancer patients (H. Takatani, H. Soda, M. Fukuda, M. Watanabe, A. Kinoshita, T. Nakamura, and M. Oka, Antimicrob. Agents Chemother. 40:988-991, 1996). The aim of this study was to clarify the relationship between rhG-CSF clearance and G-CSF receptors on circulating neutrophils. In five cancer patients receiving chemotherapy, a bolus dose of rhG-CSF (5 microg/kg) was injected intravenously during defined phases of posttreatment neutropenia and neutrophilia. Serum rhG-CSF levels were measured by a chemiluminescence enzyme immunoassay and analyzed by moment analysis. G-CSF receptors on neutrophils were detected by flow cytometry with biotinylated rhG-CSF. rhG-CSF clearance was significantly higher at neutrophilia than at neutropenia (1,497 +/- 132 versus 995 +/- 266 ml/h; P < 0.01). The percentage of G-CSF receptor-positive neutrophils, reflecting the number of G-CSF receptors per cell, was low at neutropenia without rhG-CSF therapy (44.5% +/- 22.1%) and high at neutrophilia with rhG-CSF therapy (73. 0% +/- 11.4%; P < 0.01). rhG-CSF clearance closely correlated with the percentage of G-CSF receptor-positive neutrophils (r2 = 0.91; P < 0.0001) and neutrophil count (r2 = 0.72; P < 0.005). Our results indicate that, in cancer patients receiving chemotherapy, rhG-CSF increases the number of G-CSF receptors per cell as well as circulating neutrophil counts, resulting in modulation of its own clearance.
Terashi
K
K
The Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Oka
M
M
Ohdo
S
S
Furukubo
T
T
Ikeda
C
C
Fukuda
M
M
Soda
H
H
Higuchi
S
S
Kohno
S
S
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D000078224:Lenograstim; D008175:Lung Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000097:blood*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim