Comparative analysis of the in vivo radioprotective effects of recombinant
granulocyte colony-stimulating factor (G-CSF), recombinant
granulocyte-macrophage CSF, and their combination
KG Waddick, CW Song, L Souza and FM Uckun
Department of Therapeutic Radiology-Radiation Oncology, University of
Minnesota Health Sciences Center, Minneapolis.
The purpose of the present study was to evaluate and compare the in vivo
radioprotective effects of pre-total body irradiation (TBI) conditioning
with recombinant granulocyte colony-stimulating factor (rG- CSF) and
recombinant granulocyte-macrophage CSF (rGM-CSF) in a large series of
lethally and supralethally irradiated mice. Also analyzed were the
radioprotective effects of simultaneous as well as sequential combinations
of rG-CSF and rGM-CSF. Our findings in 1,180 mice provide direct evidence
that in vivo administration of rG-CSF or rGM-CSF before TBI protects a
significant fraction of mice from the lethal effects of LD100/30 TBI. At
equivalent doses, rG-CSF displayed a more potent radioprotective activity
than rGM-CSF. Not only was rG-CSF radioprotective at much smaller doses
than rGM-CSF, the survival rate after lethal TBI was also significantly
higher in mice receiving optimally radioprotective doses of rG-CSF as
compared with mice receiving optimally radioprotective doses of rGM-CSF.
Pretreatment of mice with rGM-CSF markedly attenuated the radioprotective
affects of rG- CSF in lethally as well as supralethally irradiated mice.
Pretreatment with rG-CSF followed by rGM-CSF was slightly more effective
than rG-CSF alone in supralethally irradiated mice but not in lethally
irradiated mice. Notably, marked differences among different strains of
mice were noted regarding the optimally radioprotective doses of rG-CSF or
rGM- CSF as well as probability of survival and median survival time after
lethal or supralethal TBI. This report confirms and extends previous
studies concerning the potential of cytokines in prevention or therapy of
lethal radiation injury.
Volume 77,
Issue 11,
pp. 2364-2371,
06/01/1991
Copyright © 1991 by The American Society of Hematology
