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.