Document 0155
 DOCN  M9490155
 TI    In vitro effects of stem-cell factor or interleukin-3 on
       myelosuppression associated with AIDS.
 DT    9411
 AU    Scadden DT; Wang A; Zsebo KM; Groopman JE; Department of Medicine, New
       England Deaconess Hospital, Harvard; Medical School, Boston, MA 02215.
 SO    AIDS. 1994 Feb;8(2):193-6. Unique Identifier : AIDSLINE MED/94318202
 AB    OBJECTIVE: To determine whether the early-acting hematopoietic growth
       factors stem-cell factor (SCF) or interleukin-3 (IL-3), are able to
       overcome the bone-marrow suppressive effects of cytokines or drugs
       involved in the hematologic abnormalities that accompany HIV-1
       infection. DESIGN: In vitro colony formation assays of normal human
       bone-marrow cells exposed to the myelosuppressive drugs, zidovudine,
       interferon-alpha (IFN-alpha) and ganciclovir, or the myelosuppressive
       cytokines, tumor necrosis factor-alpha (TNF-alpha) or transforming
       growth factor-beta (TGF-beta), implicated in HIV dysmyelopoiesis.
       RESULTS: SCF (10 ng/ml) enhanced the numbers of erythroid (BFU-E)
       colonies in the presence of zidovudine or ganciclovir (P < 0.05) and
       myeloid [colony-forming unit granulocyte macrophage (CFU-GM)] colonies
       in the presence of ganciclovir or IFN-alpha (P < 0.05) relative to
       controls. IL-3 (10 ng/ml) also improved erythroid colony numbers in the
       presence of zidovudine (P < 0.05) and CFU-GM in the presence of
       IFN-alpha (P < 0.05). Neither factor consistently altered the inhibition
       of TGF-beta or TNF-alpha. The 50% inhibitory concentration (IC50) of the
       myelosuppressive agents was altered in only one setting, using IL-3 in
       the presence of zidovudine. CONCLUSIONS: These data suggest that SCF or
       IL-3 may have a therapeutic application in overcoming hematopoietic
       abnormalities associated with drugs commonly used in the care of AIDS
       patients. However, they may have less capacity to overcome the
       bone-marrow inhibitory effects of the endogenous cytokines TNF-alpha and
       TGF-beta.
 DE    Acquired Immunodeficiency Syndrome/*COMPLICATIONS/DRUG THERAPY  Bone
       Marrow Diseases/*CHEMICALLY INDUCED  Cell Division/DRUG EFFECTS
       Colony-Forming Units Assay  Comparative Study  Erythroid Progenitor
       Cells/DRUG EFFECTS  Ganciclovir/PHARMACOLOGY  Granulocyte-Macrophage
       Colony-Stimulating Factor/PHARMACOLOGY  Granulocytes  Hematopoietic Cell
       Growth Factors/*PHARMACOLOGY  Hematopoietic Stem Cells/*DRUG EFFECTS
       Human  Interferon Alfa-2a/PHARMACOLOGY  Interleukin-3/*PHARMACOLOGY
       Macrophages  Recombinant Proteins/PHARMACOLOGY  Support, U.S. Gov't,
       P.H.S.  Transforming Growth Factor beta/PHARMACOLOGY  Tumor Necrosis
       Factor/PHARMACOLOGY  Zidovudine/PHARMACOLOGY  JOURNAL ARTICLE

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