Recovery from severe hematopoietic suppression using recombinant human granulocyte-macrophage colony-stimulating factor.
The ability of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to enhance recovery of a radiation-suppressed hematopoietic system was evaluated in a nonuniform radiation exposure model using the rhesus monkey. Recombinant human GM-CSF treatment for 7 days after a lethal, nonuniform radiation exposure of 800 cGy was sufficient to enhance hematopoietic reconstitution, leading to an earlier recovery. Monkeys were treated with 72,000 U/kg/day of rhGM-CSF delivered continuously through an Alzet miniosmotic pump implanted subcutaneously on day 3. Treated monkeys demonstrated effective granulocyte and platelet levels in the peripheral blood, 4 and 7 days earlier, respectively, than control monkeys. Granulocyte-macrophage colony-forming unit (CFU-GM) activity in the bone marrow was monitored to evaluate the effect of rhGM-CSF on marrow recovery. Treatment with rhGM-CSF led to an early recovery of CFU-GM activity suggesting that rhGM-CSF acted on an earlier stem cell population to generate CFU-GM. Thus, the effect of rhGM-CSF on hematopoietic regeneration, granulocyte recovery, and platelet recovery are evaluated in this paper.
Monroy
R L
RL
Immunobiology and Transplantation Department, Naval Medical Research Institute, Bethesda, Maryland 20814-5055.
Skelly
R R
RR
Taylor
P
P
Dubois
A
A
Donahue
R E
RE
MacVittie
T J
TJ
D000818:Animals; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000528:radiation effects*; D008253:Macaca mulatta; D008297:Male; D011833:Radiation Injuries, Experimental / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013997:Time Factors
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor