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.
Gilmore
G L
GL
Western Pennsylvania Cancer Institute, Pittsburgh 15224, USA.
DePasquale
D K
DK
Fischer
B C
BC
Shadduck
R K
RK
D000818:Animals; D001854:Bone Marrow Cells; D005472:Fluorouracil / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007116:Immunization, Passive; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000502:physiology*; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008809:Mice, Inbred C3H; D009000:Monocytes / Q000166:cytology*
D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D005472:Fluorouracil