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M9490089.TXT
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1994-09-03
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Document 0089
DOCN M9490089
TI Influence of interleukin-3 (IL-3) on the hematopoietic toxicity
associated with combination anti-viral drugs (zidovudine and DDI) in
vitro using retrovirus-infected bone marrow cells.
DT 9411
AU Gallicchio VS; Hughes NK; Department of Medicine, Lucille P. Markey
Cancer Center,; Lexington, Kentucky.
SO Int J Immunopharmacol. 1994 Apr;16(4):359-66. Unique Identifier :
AIDSLINE MED/94321089
AB The drug zidovudine (AZT), a synthetic thymidine analog, has been used
in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical
use of zidovudine has been associated with the development of
hematopoietic toxicity manifested by anemia, neutropenia, and on
occasion thrombocytopenia. This toxicity has resulted in the development
of alternative dideoxynucleoside drugs capable of exerting anti-viral
potency while minimizing the risk for inducing organ toxicities. One
such dideoxynucleoside drug is 2',3'-dideoxyinosine (ddI). Clinical
trials are currently evaluating the effect of combination anti-viral
drug treatment such as zidovudine plus ddI. We report here the results
of studies designed to evaluate the effect of interleukin-3 (IL-3) on
its ability to influence the hematopoietic toxicity associated with
zidovudine and ddI following combination with retroviral-infected murine
bone marrow cells. Toxicity was evaluated by quantitating several
classes of hematopoietic progenitor stem cells such as
granulocyte-macrophage (CFU-GM), erythroid (CFU-E and BFU-E) and
megakaryocyte (CFU-Meg). Dose-escalation IL-3 provided protection of
anti-viral drug induced suppression of progenitor cells when combined in
the presence of the ID50 concentration of either zidovudine or ddI;
however, when zidovudine and ddI were combined, IL-3 was less effective
in providing protection against drug-induced toxicity at any
concentration examined. These results indicate that IL-3 is effective in
reducing anti-viral drug-induced hematopoietic toxicity associated with
single-agent use; however, IL-3 is less effective when such drugs are
used in combination.
DE Animal Antiviral Agents/*TOXICITY Bone Marrow/*CYTOLOGY/DRUG
EFFECTS/MICROBIOLOGY Didanosine/TOXICITY Drug Interactions Female
Hematopoiesis/*DRUG EFFECTS Hematopoietic Stem Cells/DRUG EFFECTS
IgM/BIOSYNTHESIS Interleukin-3/*PHARMACOLOGY Mice Mice, Inbred C57BL
Retroviridae Infections/*PHYSIOPATHOLOGY Stem Cells/DRUG EFFECTS
Support, U.S. Gov't, Non-P.H.S. Zidovudine/TOXICITY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).