       Document 0397
 DOCN  M9630397
 TI    Azidothymidine and interferon-alpha in vitro effects on hematopoiesis:
       protective in vitro activity of IL-1 and GM-CSF.
 DT    9603
 AU    Castello G; Mela G; Cerruti A; Mencoboni M; Lerza R; Department of
       Internal Medicine, University of Genova, Italy.
 SO    Exp Hematol. 1995 Dec;23(13):1367-71. Unique Identifier : AIDSLINE
       MED/96103541
 AB    Preclinical and clinical studies with an azidothymidine
       (AZT)/interferon-alpha (IFN-alpha) combination resulted in a marked and
       synergistic antiretroviral activity. The administration of the two drugs
       in HIV-seropositive patients affected with Kaposi's sarcoma, however,
       induced neutropenia, thrombocytopenia, and, in some cases, anemia. A
       possible means to improve the therapeutic index of AZT and/or IFN-alpha
       in AIDS patients could be the addition of hematopoietic growth factors.
       In vitro activity of cytokines on the hematotoxicity of the
       AZT-IFN-alpha association has not yet been studied. We have performed an
       in vitro study to evaluate the toxicity of AZT, IFN-alpha, or both on
       peripheral blood hematopoietic progenitors (CFU-GM and BFU-E) and to
       assess the activity of interleukin 1 (IL-1), granulocyte-macrophage
       colony-stimulating factor (GM-CSF), or both in modifying AZT-IFN-alpha
       hematotoxicity. Results indicate that AZT, IFN-alpha, and combinations
       of the two have a dose-dependent inhibitory effect on the in vitro
       growth of peripheral blood hematopoietic progenitors. Combinations of
       AZT and IFN-alpha inhibited CFU-GM and BFU-E proliferation in an
       additive manner. Neither IL-1 nor GM-CSF alone was able to induce a
       significant reduction of AZT-induced damage. Only the addition to the
       cultures of both cytokines partially curbed the antiproliferative
       activity of AZT at low dosages.
 DE    Antimetabolites/PHARMACOLOGY/*TOXICITY  Cell Division/DRUG EFFECTS
       Cells, Cultured  Colony-Forming Units Assay  Comparative Study  Drug
       Interactions  Erythroid Progenitor Cells/DRUG EFFECTS
       Granulocyte-Macrophage Colony-Stimulating Factor/*PHARMACOLOGY
       Hematopoiesis/*DRUG EFFECTS  Hematopoietic Stem Cells/*DRUG EFFECTS
       Human  HIV Infections/DRUG THERAPY  Interferon
       Alfa-2a/PHARMACOLOGY/*TOXICITY  Interleukin-1/*PHARMACOLOGY  Support,
       Non-U.S. Gov't  Zidovudine/PHARMACOLOGY/*TOXICITY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

