An increase in peripheral blood progenitor cells in primates by coadministration of recombinant human interleukin 6 and recombinant human granulocyte colony-stimulating factor.
BACKGROUND
We recently demonstrated that coadministration of recombinant human interleukin 6 (rhIL-6) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in mice synergistically increases peripheral blood stem cells (PBSC), which can rescue lethally irradiated recipient mice. However, there is little information about the effect of coadministration of rhIL-6 and rhG-CSF on PBSC in a primate system.


METHODS
In cynomolgus monkeys, rhG-CSF (5 microg/kg day) alone was administered for 5 days (first cycle). After the wash-out period, rhIL-6 (0, 10, or 20 microg/kg/day) and rhG-CSF were coadministered for 5 days (second cycle).


RESULTS
Total peripheral colony-forming cells levels were increased earlier by coadministration of rhIL-6 and rhG-CSF than by the administration of rhG-CSF alone. The maximum level in the coadministration cycle was obtained on day 5, and a high level was obtained for a further 3 days after cessation. The maximum number of peripheral total colony-forming cells in the coadministration cycle was a mean of 2.12-fold (range 1.38 to 3.35) higher than that in the rhG-CSF alone cycle. Coadministration also increased the peripheral mixed colony-forming units by a mean of 3.62-fold (range 1.02 to 5.52). Interestingly, monkeys that showed a low response to the administration of rhG-CSF alone also had a higher response to the coadministration. No significant difference was observed between the two cycles of administration of rhG-CSF alone.


CONCLUSIONS
These findings suggest that coadministration of rhIL-6 and rhG-CSF may be useful for clinical PBSC collection.
Suzuki
H
H
Central Research Laboratories, Ajinomoto Co., Inc., Yokohama, Japan.
Ikebuchi
K
K
Wada
Y
Y
Okano
A
A
Nakamiya
T
T
Akiyama
Y
Y
Sawada
T
T
Asano
S
S
Nakahata
T
T
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001772:Blood Cell Count / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D015850:Interleukin-6 / Q000494:pharmacology*; D007958:Leukocyte Count; D008252:Macaca fascicularis; D010919:Placebos; D011994:Recombinant Proteins / Q000494:pharmacology; D012709:Serum Albumin / Q000378:metabolism
D015850:Interleukin-6; D010919:Placebos; D011994:Recombinant Proteins; D012709:Serum Albumin; D016179:Granulocyte Colony-Stimulating Factor; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase