In vivo evaluation of the anemia induced by azidothymidine (AZT) in a murine model of AIDS.
Azidothymidine (AZT) induces severe anemia in patients with acquired immune deficiency syndrome (AIDS). To evaluate the mechanism of anemia in immune-suppressed animals, a murine model of AIDS (MAIDS), caused by infection with LP-BM5 murine leukemia virus (LP-BM5 MuLV) was used at early and late stages of the disease. AZT-induced anemia was dose- and time-dependent. An increased percentage of erythroblasts in bone marrow was observed, with an increased ratio of early to late erythroblasts in both disease stages. Increases in splenic erythroid burst-forming units (BFUe) were observed in early-stage AZT-treated mice. Mean plasma erythropoietin (EPO) levels were increased by AZT in both groups in a dose-dependent manner and were inversely proportional to hematocrit values. These data suggest that the anemia induced by AZT stimulated a response by immature erythroid elements, but that the maturation or survival of early erythroblasts may be impaired.
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University of Maryland Cancer Center, Baltimore 21201.
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D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000740:Anemia / Q000209:etiology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000096:biosynthesis; D005260:Female; D006400:Hematocrit; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012156:Reticulocytes / Q000187:drug effects; D013997:Time Factors; D015215:Zidovudine / Q000009:adverse effects*
D004921:Erythropoietin; D015215:Zidovudine