Hemopoietic function after use of IL-1 with chemotherapy or irradiation.
IL-1 has putative chemo- and radioprotective properties, but its effects on primitive hemopoietic stem cell (PHSC) and early multilineage precursor function when given with these modalities is unknown. C57BL6/J (B6) mice, given IL-1 20 h before cyclophosphamide (200 mg/kg for four biweekly doses) or before irradiation (500 cGy), were sacrificed after 4 wk. Their marrow was used as donor cells, and that from B6-Hbb(dGpi1a) (B6-GPI) mice was used as competitor cells in competitive repopulation. Percentages of B6 cells were measured at 30 and 150 days. Stem cell numbers were estimated using binomial statistics. IL-1 alone did not affect stem cell function. As expected, significant declines in early multilineage precursor and PHSC function occurred with chemotherapy and radiation alone. IL-1 with chemotherapy led to exacerbation of these losses in function and numbers (p < 0.05). A similar reduction in function occurred using IL-1 before irradiation. In summary, IL-1 with chemotherapy or radiation worsened chemotherapy- and radiation-induced functional damage to PHSC and other hemopoietic precursors, suggesting that improvements in survival do not necessarily translate into preservation of hemopoietic function.
Gardner
Renee V
RV
Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. rgardn@lsuhuc.edu
McKinnon
Evangeline
E
Poretta
Connie
C
Leiva
Lily
L
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D019070:Cell Lineage / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects*; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000627:therapeutic use; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D011828:Radiation Chimera / Q000276:immunology; D016019:Survival Analysis
D007375:Interleukin-1; D003520:Cyclophosphamide