Several hematopoietic cytokines have been investigated for their poten
tial to provide protection from the lethal consequences of bone marrow
aplasia after total body irradiation (TBI). Some can increase the dos
e of irradiation tolerated by the animals; none allow endogenous recov
ery after doses such as administered in clinical blood or marrow trans
plantation. We tested the radioprotective potential of FLT-3 ligand, a
n early acting hematopoietic cytokine, alone and in combination with a
late acting cytokine, granulocyte-colony stimulating factor (G-CSF).
Adult outbred New Zealand White rabbits were submitted to TBI of 1,200
or 1,400 cGy by a Co-60 source. Recombinant human (rh) FLT-3 ligand a
t a dose of 500 mu g/kg and/or rhG-CSF at a dose of 10 mu g/kg were ad
ministered for 14 days subcutaneously daily, beginning either 2 days b
efore or the day after TBI. All control animals given no growth factor
s died of aplasia at day 10 (range, 5 to 16). All 8 animals given G-CS
F had severe aplasia and 7 died at day 8 (range, 5 to 10); 1 animal su
rvived, with G-CSF being administered before TBI. In contrast, 11 of 1
2 animals given FLT-3 ligand, with or without G-CSF, survived. Radiopr
otection was best in the group given FLT-3 ligand together with G-CSF
before TBI. In these animals median platelet counts were never <10 x 1
0(9)/L and median white blood cell counts never <0.5 x 10(9)/L. These
data show that hematopoietic recovery can occur after 1,400 cGy TBI in
rabbits, if protected by FLT-3 ligand, and suggest a radioprotective
clinical potential of this cytokine. (C) 1998 by The American Society
of Hematology.