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1996-02-27
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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).