Document 0237
 DOCN  M9650237
 TI    Inhibition of human immunodeficiency virus type 1 multiplication by
       transforming growth factor beta 1 and AZT in HIV-1-infected myeloid
       cells.
 DT    9605
 AU    McKiel V; Gu Z; Wainberg MA; Hiscott J; Lady Davis Institute for Medical
       Research, Jewish General; Hospital, Department of Microbiology and
       Immunology, Montreal,; Quebec, Canada.
 SO    J Interferon Cytokine Res. 1995 Oct;15(10):849-55. Unique Identifier :
       AIDSLINE MED/96122471
 AB    Myeloid cells are important reservoirs of HIV-1 infection. In response
       to pathogenic agents, macrophages secrete inflammatory cytokines that
       can modulate viral replication and contribute to AIDS pathogenesis.
       Because HIV replication is dependent on cellular activation,
       immunosuppressive cytokines that deactivate macrophages and T cells may
       be important modulators of an antiviral effect. We tested the anti-HIV
       potential of the immunosuppressive cytokine-transforming growth factor
       beta (TGF-beta 1) alone and in combination with AZT in a new
       monomyeloblastic model of HIV-1 infection. The PLB-985 cell model was
       infected with HIV IIIB strain, and the course of HIV-1 infection and
       replication was monitored by reverse transcriptase assay, p24
       immunofluorescence, and northern blot analysis of HIV-1-specific mRNA.
       TGF-beta 1 as a single agent had no effect on the multiplication of
       HIV-IIIB in de novo-infected PLB 985 monomyeloblastic cells. However,
       cotreatment with TGF-beta 1 and AZT synergistically slowed virus
       multiplication within the first week following infection, as determined
       by reverse transcriptase measurement, p24 antigen detection, and
       northern blot analysis of viral RNA. The synergistic actions of TGF-beta
       1 and AZT were also observed in PLB 985 cells infected with an
       AZT-resistant strain of HIV-1 (HIV 1393). Synergism between nucleoside
       analogs and cytokines may be an important therapeutic approach to HIV-1
       infection. Elucidation of the role of cytokines in controlling the
       degree of HIV multiplication may have an impact on both clinical
       treatments and understanding the progression to AIDS.
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY/PATHOLOGY  Antiviral
       Agents/*PHARMACOLOGY  Cell Line  Drug Therapy, Combination  Human
       HIV-1/*GROWTH & DEVELOPMENT  Immunosuppressive Agents/*PHARMACOLOGY
       Leukemia, Myelomonocytic, Acute/PATHOLOGY  Leukocytes, Mononuclear/DRUG
       EFFECTS/VIROLOGY  Support, Non-U.S. Gov't  Transforming Growth Factor
       beta/*PHARMACOLOGY  Tumor Cells, Cultured  Zidovudine/*PHARMACOLOGY
       JOURNAL ARTICLE

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