Timing of recombinant human granulocyte colony-stimulating factor administration on neutropenia induced by cyclophosphamide in normal mice

Abstract

Summary The effects of altering the timing of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration on neutropenia induced by cyclophosphamide (CPA) were studied experimentally in a mouse model. Experimental mice were divided into three groups: (a) treatment with rhG-CSF after CPA administration (post-treatment group); (b) treatment with rhG-CSF both before and after CPA administration (pre-and post-treatment group); and (c) treatment with saline after CPA administration (control group). The results were as follows. Mice receiving rhG-CSF on the 2 days preceding CPA treatment, in which progenitor cell counts outside the S-phase when CPA was administered were the lowest of all the groups, showed accelerated neutrophil recovery but decreased neutrophil nadirs compared with the control group despite rhG-CSF treatment. The pre-and post-treatment group, consisting of mice who received rhG-CSF treatment on days -4 and -3 before CPA treatment, and in which progenitor cell counts when CPA was administered were increased to greater levels than in the other groups, showed remarkably accelerated neutrophil recovery and the greatest increase in the neutrophil nadirs of all the groups. These results suggested that the kinetics of progenitor cell populations when chemotherapeutic agents were administered seemed to play an important role in neutropenia after chemotherapy, and that not only peripheral neutrophil cell and total progenitor cell counts but also progenitor cell kinetics should be taken into consideration when administering rhG-CSF treatment against the effects of chemotherapy.

The Effect of Immunosuppression on Aortic Dilatation in a Rat Aneurysm Model

“…6,7 To these agents we added cyclophosphamide to reduce the number of neutrophils and inhibit their function, 26 as neutrophils play an important role in the aortic inflammatory infiltration in this model. 14,16,23 Using single-drug immunosuppression, Dobrin et al 17 evaluation, and drug regimen from their experimental protocol, we noted similar results with respect to cellular infiltration and aortic dilatation; however, the histological findings were different.…”

Effectiveness of cytopenia prophylaxis for different filgrastim and pegfilgrastim schedules in a chemotherapy mouse model

“…Bauhofer and colleagues57 investigated the effect of G-CSF schedules in a septic rat model. Misaki and colleagues58 analysed different timings of G-CSF prior to CP application. Yankelevich and colleagues59 addressed the effect of timing of filgrastim on bone marrow cellularity but did not measured the time course in the nadir phase of circulating cells.…”

Retinoid agonist Am80-enhanced neutrophil bactericidal activity arising from granulopoiesis in vitro and in a neutropenic mouse model

“…Using a neutropenic mouse model induced by a single dose of CPA, as described, 31,32 we tested whether in vivo mobilized neutrophils by Am80 indeed possess the same greater neutrophil immunity against bacterial infection than those by G-CSF, as observed in the ex vivo model (Figures 4, 6). We found that a severe reduction of both WBCs and neutrophils occurred in all experimental mice 3 days after injection of CPA, compared with control mice ( Figure 7A).…”

“…Twenty female C57BL6/J mice (The Jackson Laboratory), aged 6 to 8 weeks, were randomly divided into 1 control and 3 experimental groups. To create neutropenic mouse model, as described, 31,32 experimental mice received a single 200 mg/kg intraperitoneal dose of cyclophosphamide (CPA; Baxter Healthcare) at day 0, whereas control mice with PBS. To induce neutrophil recovery, experimental mice at day 3 were treated with either 250 g/kg G-CSF by subcutaneous injection 32 or 5 mg/kg Am80 or PBS intraperitoneally for consecutive 2 or 6 days.…”

“…To create neutropenic mouse model, as described, 31,32 experimental mice received a single 200 mg/kg intraperitoneal dose of cyclophosphamide (CPA; Baxter Healthcare) at day 0, whereas control mice with PBS. To induce neutrophil recovery, experimental mice at day 3 were treated with either 250 g/kg G-CSF by subcutaneous injection 32 or 5 mg/kg Am80 or PBS intraperitoneally for consecutive 2 or 6 days. Each 50 L of PB was collected from the tail vein every other day for monitoring the baseline of leukocytes (WBCs) and neutrophils with Vetscan HM5 (Abaxis).…”