Protective effects of IL-1 on human hematopoietic progenitor cells treated in vitro with 4-hydroperoxycyclophosphamide.
Based on recently published data, IL-1 has been shown to provide radioprotective effects when given to mice 20 h before a lethal dose of irradiation and to enhance granulocyte recovery in mice treated with cyclophosphamide. In this study, we have investigated whether IL-1 can provide protection for human bone marrow colony-forming cells treated with high doses of 4-hydroperoxycyclophosphamide (4-HC), a potent derivative of cyclophosphamide. We have established an in vitro model system which demonstrates that prior incubation with IL-1 protects early human hematopoietic progenitor cells from the lethal effects of high doses of 4-HC. These early progenitors give rise to blast cell colonies which appear late in the culture and are characterized by their ability to give rise to different types of secondary colonies when replated. Furthermore, prior incubation with IL-1 was shown not to protect HL-60 or K562 leukemic cells from the lethal effects of 4-HC. We conclude that IL-1 is able to protect early human hematopoietic progenitors from a non-cell cycle-specific chemotherapeutic agent such as 4-HC, whereas providing no protection for the leukemic cell lines HL-60 and K562.
Moreb
J
J
Department of Medicine, University of Florida, Gainesville 32610.
Zucali
J R
JR
Gross
M A
MA
Weiner
R S
RS
D000328:Adult; D001853:Bone Marrow / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000627:therapeutic use*; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology
D007375:Interleukin-1; D003520:Cyclophosphamide; C011272:perfosfamide