Temporal recovery of short-term repopulating HSC subpopulations in marrow following schedule-dependent administrations of IL-1 alpha and M-CSF.
Studies were carried out to establish the temporal effects of abbreviated administrations of IL-1 and IL-1 plus M-CSF as rescue agents on multipotential and short-term repopulating hematopoietic stem cell (HSC) subpopulations in murine marrow treated with a myelosuppressive dose of 150 mg/kg 5-FU. The recovery kinetics for high-proliferative-potential colony-forming cells (HPP-CFC), CFU-S8 and -S12, and both CFU-M and CFU-G compartments were monitored over a 14-day interval in 5-FU-treated bone marrow (FUBM) following daily cytokine injections over a 4-day interval. Both IL-1 and the coadministration of IL-1 and M-CSF rapidly enhanced the recovery of the HPP-CFC in FUBM to supranormal levels and maintained these levels for extended intervals. Moreover, since M-CSF was unable to influence the recovery of the HSC subpopulations in FUBM by itself, the results of the two cytokines amounted to a synergistic effect on the recovery of the HPP-CFC in FUBM and a reduction of severe neutropenia in the myelosuppressed animal. Scheduling studies demonstrated that these synergistic effects were restricted to those schedules in which M-CSF was coadministered with IL-1 during the first 2 days of cytokine rescue. Finally, the recovery curves generated for the HSC and CFU-M subpopulations in response to IL-1 (with or without M-CSF) also suggest that these cytokines may conceivably alter the normal balance between proliferation and differentiation within CFU-S8 and -S12 during the accelerated recovery of hematopoiesis in FUBM.
Kovacs
C J
CJ
Department of Radiation Oncology, Leo Jenkins Cancer Center, East Carolina University School of Medicine, Greenville, NC 27858, USA.
Evans
M J
MJ
Roberts
C
C
Harrell
J
J
Abernathy
R
R
Gooya
J
J
Johnke
R M
RM
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012016:Reference Values; D013997:Time Factors
D007375:Interleukin-1; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D005472:Fluorouracil