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).