Interleukin-6 and granulocyte colony-stimulating factor synergistically increase peripheral blood progenitor cells in myelosuppressive mice.
We previously reported a successful peripheral blood stem cell harvest by co-administration of recombinant human (rh) interleukin-6 (IL-6) and rh granulocyte colony-stimulating factor (G-CSF) in normal mice. In the present study, to evaluate further the utility of this observation for autologous peripheral blood stem cell transplantation, we examined the effects of rhIL-6 and rhG-CSF on peripheral blood granulocyte-macrophage colony-forming units (CFU-GM) in carboplatin (CBDCA)-induced and irradiation-induced myelosuppressive mouse models. After CBDCA administration, blood cell counts decreased to the nadir, and then recovered to a normal level. In this recovery phase, the peripheral CFU-GM level increased to 3.8-fold higher than the pretreatment level. Administration of rhIL-6 (10 microgram/day) alone induced a 40-fold increase in peripheral CFU-GM from the normal level at day 14. In combination with rhG-CSF (0.35 microgram/day), which alone induced a 74-fold increase, rhIL-6 synergistically increased the CFU-GM level by 1200-fold. In irradiated mice, similar results were observed. Administration of rhIL-6 at 3 and 10 microgram/day significantly increased CFU-GM. Interestingly, in combination with rhG-CSF, a lower dose of rhIL-6 (1 microg/day) could induce CFU-GM increase. We also examined CFU-GM distribution in bone marrow, spleen and peripheral blood. Cytokine administration induced not only a change of CFU-GM distribution, but also an increase in total CFU-GM counts per mouse. These results suggest that co-administration of rhIL-6 and rhG-CSF may be useful for autologous peripheral blood stem cell transplantation.
Suzuki
H
H
Central Research Laboratories, Ajinomoto Co., Inc., Totsuka-ku, Yokohama.
Okano
A
A
Ejima
C
C
Konishi
A
A
Akiyama
Y
Y
Ozawa
K
K
Asano
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D001772:Blood Cell Count / Q000187:drug effects / Q000528:radiation effects; D016190:Carboplatin / Q000633:toxicity; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL
D000970:Antineoplastic Agents; D015850:Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor; D016190:Carboplatin