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, Oh, 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 mu g/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 (r(2) = 0.91; P < 0.0001) and neutrophil count (r(2) = 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.