Acceleration of hemopoietic recovery in dogs after extended-field partial-body irradiation by treatment with colony-stimulating factors: rhG-CSF and rhGM-CSF.

Abstract

The influence of treatment with the two colony-stimulating factors, rhG-CSF and rhGM-CSF, on the hemopoietic recovery in aplastic bone marrow sites after extended-field irradiation was studied in a canine model. The dogs received irradiation of the cranial part of their body with a single dose of 11.7 Gy, comprising approximately 72% of the total bone marrow mass. Anatomically this type of exposure corresponds to upper body irradiation (UBI) as employed under clinical conditions. Treatment with both the CSFs was employed for 7 days by daily injections of 30 microg/kg, starting 24 hr after irradiation. Treatment with rhGM-CSF did not completely prevent the initial decrease of the granulocyte counts, but caused an accelerated, though incomplete, recovery in the period from day 5 to day 15. In contrast, treatment with rhG-CSF caused two phases of granulocytosis and an early recovery to normal levels at day 11 after irradiation. Treatment with rhG-CSF, but not with rhGM-CSF, was associated with a strong supra-normal increase of progenitor cells in the blood within the first 8 days and an accelerated hemopoietic recovery in the irradiated sites particularly within the first 7 days after the exposure. These results indicate that under conditions of partial-body irradiation short term treatment with G-CSF is superior to GM-CSF in initiating the hemopoietic recovery on the basis of endogenous stem cell seeding.