[In-vivo enhancement of neutrophil function by administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in cyclophosphamide (CPA) treated mice].
The in-vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the number and function (phagocytosis and superoxide production) of peripheral neutrophils were studied in time sequence in cyclophosphamide (CPA) treated mice. The neutrophil function was evaluated by the phagocytosis of fluorescent particles, analyzing the number of fluorescence-positive cells and the fluorescence intensity of each neutrophil by flow cytometry and also by the superoxide production, measuring chemiluminescence of the leukocyte suspension by a photometer. In CPA-treated (100 mg/kg) mice, the neutrophil function including both the phagocytosis and the superoxide production declined significantly (p less than 0.01) as the peripheral neutrophil count (PNC) decreased, reached the nadir on the same day as PNC and returned to the normal level 8 days after first CPA treated day (day 0). When rhG-CSF (100 micrograms/kg) was administered subcutaneously daily for 5 consecutive days initiating at day 1, a decrease in PNC and a decline in the neutrophil function were prevented and a significant (p less than 0.05-p less than 0.01) increase of PNC was observed after day 4. In addition, the function of increased neutrophils was significantly (p less than 0.05-p less than 0.01) enhanced after day 4 and even at day 3, when an increase in PNC was not observed yet. The study shows that rhG-CSF appears to enhance neutrophil function by a direct effect on mature neutrophils, which have been impaired by CPA at the phase of progenitor cells in the bone marrow and subsequently have appeared in the peripheral blood and that rhG-CSF is effective on the impaired host defense mechanism in CPA-treated mice, improving not only drug-induced neutropenia but also the deteriorated function of neutrophils.
Yoshida
M
M
Department of Urology, Faculty of Medicine, University of Tokyo.
D000818:Animals; D003520:Cyclophosphamide / Q000009:adverse effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D011994:Recombinant Proteins; D013481:Superoxides; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide