Sustained elevation of platelet counts by long-term azidothymidine treatment of immunosuppressed mice.
Azidothymidine (AZT) has been demonstrated to increase platelet counts in patients suffering from acquired immunodeficiency syndrome (AIDS). However, the ability of long-term AZT treatment to sustain increases in platelet counts is controversial. We have recently demonstrated that AZT elevates the levels of circulating platelets in both normal C57BL/6 mice and mice made immunodeficient by infection with LP-BM5 murine leukemia virus (MAIDS mice). We therefore studied the effect of long-term AZT administration on platelet formation in both normal and MAIDS mice. Peripheral blood indices, levels of femoral and splenic megakaryocyte colony forming units (CFU-MK), and plasma levels of cytokines important in platelet formation-interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF)--were examined. Platelet counts remained elevated throughout a 120-day AZT treatment period. Splenic CFU-MK were not significantly changed in MAIDS mice, except at day 15 when they were elevated. Splenic CFU-MK were significantly decreased in normal mice at days 8 and 120, and increased at day 30. Bone marrow CFU-MK were increased by AZT treatment at all time points tested in both normal and MAIDS mice. Plasma levels of GM-CSF were unchanged by AZT treatment in both normal and MAIDS mice. Plasma levels of IL-6 were unchanged in AZT-treated normal mice but decreased in AZT-treated MAIDS mice. These results indicate that long-term AZT treatment maintains elevated levels of platelets in both normal and MAIDS mice and affects CFU-MK colony formation. Our studies add to a growing body of work suggesting that AZT can ameliorate thrombocytopenia associated with HIV disease.
Chow
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University of Maryland Cancer Center, Baltimore 21201.
Chen
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Hamburger
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D000818:Animals; D003114:Colony-Forming Units Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008533:Megakaryocytes / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000188:drug therapy; D010976:Platelet Count / Q000187:drug effects*; D013997:Time Factors; D015215:Zidovudine / Q000494:pharmacology* / Q000627:therapeutic use
D015850:Interleukin-6; D015215:Zidovudine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor