Failure of stem cell factor to ameliorate AZT-induced anemia in immunodeficient mice.
Recent attempts to reduce 3' azido-3' deoxythymidine (AZT)-induced anemia in AIDS patients have focused both on AZT dose reduction and on the use of recombinant cytokines. The newly cloned cytokine stem cell factor (SCF) is a potent regulator of hematopoietic progenitor cell proliferation. Therefore, we attempted to ameliorate AZT-induced anemia using stem cell factor (SCF) in the LP-BM5 murine leukemia virus-induced model of AIDS (MAIDS). SCF was administered with oral AZT for up to 1 month, and effects on erythropoiesis examined. SCF alone increased both splenic BFU-E and CFU-E. AZT alone also increased the number of splenic BFU-E and CFU-E. SCF, administered to AZT-treated MAIDS mice, did not further enhance these increases. SCF increased bone marrow cellularity in AZT-treated MAIDS mice. However, the total number of bone marrow BFU-E was unaffected. In contrast, AZT, SCF, and the combination significantly decreased bone marrow CFU-E. SCF alone increased the absolute numbers of peripheral blood reticulocytes in MAIDS mice, but did not increase reticulocyte numbers in AZT-treated mice. SCF did not significantly increase hematocrits in either control or AZT-treated mice. Further studies are needed to maximize the differentiating capacity of the enlarged erythroid progenitor cell pool induced by SCF.
Hamburger
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AW
University of Maryland Cancer Center, Department of Pathology, Baltimore 21201.
Zsebo
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Chow
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D000740:Anemia / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D003114:Colony-Forming Units Assay; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D006400:Hematocrit; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D009052:Leukemia Virus, Murine; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D019089:Stem Cell Factor; D015215:Zidovudine / Q000627:therapeutic use / Q000633:toxicity*
D016298:Hematopoietic Cell Growth Factors; D019089:Stem Cell Factor; D004921:Erythropoietin; D015215:Zidovudine