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 μg/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 μg/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 μg/day significantly increased CFU‐GM. Interestingly, in combination with rhG‐CSF, a lower dose of rhIL‐6 (1 μg/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.