Enhancement of monocytopoiesis by granulocyte colony-stimulating factor: evidence for secondary cytokine effects in vivo.

Granulocyte colony-stimulating factor (G-CSF) is used with increasing frequency to reduce the neutropenic interval following dose-intensive chemotherapy. In mice, exogenous G-CSF reduces neutrophil recovery after 5-fluorouracil (5-FU) treatment from 14 to 8 days. G-CSF treatment also enhances recovery of blood monocytes; colony assays show increased numbers of macrophage and granulocyte-macrophage progenitors (CFU-M and CFU-GM) in the marrow. This unexpected effect of G-CSF treatment is dependent on endogenous M-CSF; antiserum to murine M-CSF inhibits both peripheral monocyte and monocytic progenitor recovery without affecting neutrophil or CFU-GM recovery. Conversely, the effect of M-CSF depletion is seen only in G-CSF-stimulated recovery; monocyte levels in mice treated with antiserum to M-CSF after 5-FU are indistinguishable from mice given 5-FU alone. No synergy between G-CSF and M-CSF can be demonstrated in vitro with either normal or 5-FU-treated marrow, indicating this G-CSF/M-CSF interaction must be indirect. These results reveal an unpredicted beneficial effect of G-CSF treatment on monocyte recovery and a role for endogenous M-CSF in rebound hematopoiesis.