The effect of recombinant GM-CSF on the recovery of monkeys transplanted with autologous bone marrow.
The regulatory function of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte production in vivo was evaluated in an autologous bone marrow transplantation model using rhesus monkeys. Monkeys were exposed to 9.0 Gy total body irradiation and then transplanted with 5.0 x 10(7) low-density bone marrow cells/kg. Alzet miniosmotic pumps were subcutaneously implanted to deliver rhGM-CSF at a rate of 50,400 U/kg/d. Minipumps, containing either rhGM-CSF or saline, were implanted between zero and five days after transplantation for seven days. Kinetic recoveries of peripheral blood cells after either saline or rhGM-CSF treatment were compared. Treatment with rhGM-CSF accelerated the recovery of neutrophils. Neutrophils in rhGM-CSF-treated animals recovered to 80% (3.4 x 10(3)/mm3) pre-irradiation control levels by day 20, in comparison with only 33% (0.9 x 10(3)/mm3) recovery for saline control monkeys. In addition, the recovery of neutrophils was enhanced over that of the controls, reaching 140% v 70% on day 30. Another prominent feature of rhGM-CSF-treated monkeys was the accelerated recovery of platelets, reaching near 50% normal levels by day 24 in comparison with 20% of normal levels for controls. The infusion of rhGM-CSF was shown to be an effective regulator of early hematopoietic regeneration, leading to the accelerated recovery of both neutrophils and platelets and then providing a consistent sustained increase of neutrophils even in the absence of rhGM-CSF.
Monroy
R L
RL
Immunobiology and Transplantation Department, Naval Medical Research Institute, Bethesda, MD 20814-5055.
Skelly
R R
RR
MacVittie
T J
TJ
Davis
T A
TA
Sauber
J J
JJ
Clark
S C
SC
Donahue
R E
RE
D000818:Animals; D016026:Bone Marrow Transplantation; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D004341:Drug Evaluation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use*; D007700:Kinetics; D008253:Macaca mulatta; D008264:Macrophages / Q000166:cytology; D008297:Male; D009000:Monocytes / Q000166:cytology; D011994:Recombinant Proteins / Q000627:therapeutic use*; D014182:Transplantation, Autologous
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor