       Document 0433
 DOCN  M9640433
 TI    Interleukin 1 induces HIV-1 expression in chronically infected U1 cells:
       blockade by interleukin 1 receptor antagonist and tumor necrosis factor
       binding protein type 1.
 DT    9604
 AU    Granowitz EV; Saget BM; Wang MZ; Dinarello CA; Skolnik PR; Department of
       Medicine, New England Medical Center Hospitals,; Boston, MA 02111, USA.
 SO    Mol Med. 1995 Sep;1(6):667-77. Unique Identifier : AIDSLINE MED/96091390
 AB    BACKGROUND: Cytokines and cytokine antagonists modulate human
       immunodeficiency virus (HIV) replication in vitro and may be involved in
       HIV disease pathogenesis. An understanding of these cytokine networks
       may suggest novel treatment strategies for HIV-seropositive persons.
       MATERIALS AND METHODS: U1 cells, a chronically infected promonocytic
       cell line, were stimulated with interleukin 1 alpha (IL-1 alpha), IL-1
       beta or tumor necrosis factor (TNF) for 24 hr. The effects of these
       cytokines, and of anti-IL-1 receptor type 1 and type 2 (IL-1RI and II)
       antibody, IL-1 receptor antagonist (IL-1Ra), and recombinant human TNF
       binding protein type 1 (rhTBP-1, a form of TNF receptor p55), on HIV-1
       replication, as measured by ELISA for HIV-1 p24 antigen, were
       determined. The effects of IL-1 and IL-1Ra on nuclear factor-kappa B
       (NF-kappa B) DNA binding activity, as measured by electrophoretic
       mobility shift assays, were also determined. RESULTS: IL-1 alpha and
       IL-1 beta increased p24 antigen production in a concentration-dependent
       manner. IL-1Ra completely, and rhTBP-1 partially, suppressed
       IL-1-induced p24 antigen production. IL-1 increased NF-kappa B DNA
       binding activity and IL-1Ra blocked this effect. Since IL-1Ra blocks
       IL-1 from binding to both the IL-1RI and Il-1RII, monoclonal antibodies
       directed against each receptor were used to ascertain which IL-1R
       mediates IL-1-induced HIV-1 expression. Antibody to the IL-1RI reduced
       IL-1-induced p24 antigen production. Although anti-IL-1RII antibody
       blocked the binding of 125IL-1-1 alpha to U1 cells by 99%, this antibody
       did not affect IL-1-induced p24 antigen production. IL-1 beta enhanced
       TNF alpha-induced HIV expression when added before or simultaneously
       with TNF alpha. CONCLUSIONS: IL-1 induces HIV-1 expression (via the
       IL-1RI) and NF-kappa B activity in U1 cells. These effects are blocked
       by IL-1Ra and partially mediated by TNF. IL-1 enhances TNF alpha-induced
       HIV replication in U1 cells.
 DE    Analysis of Variance  Animal  Antibodies, Monoclonal  Cell Line
       Comparative Study  CHO Cells  Dose-Response Relationship, Drug
       DNA-Binding Proteins/*PHARMACOLOGY  Hamsters  Human  HIV Core Protein
       p24/BIOSYNTHESIS  HIV Seropositivity/THERAPY  HIV-1/DRUG
       EFFECTS/*PHYSIOLOGY  Interleukin-1/ANTAGONISTS & INHIB/*PHARMACOLOGY
       Kinetics  Lymphoma, Large-Cell  Mice/IMMUNOLOGY  NF-kappa B/METABOLISM
       Recombinant Proteins/ANTAGONISTS & INHIB/PHARMACOLOGY
       Sialoglycoproteins/*PHARMACOLOGY  Support, U.S. Gov't, P.H.S.
       Tetradecanoylphorbol Acetate/PHARMACOLOGY  Time Factors  Transfection
       Tumor Cells, Cultured  Tumor Necrosis Factor/PHARMACOLOGY  Virus
       Replication/*DRUG EFFECTS  JOURNAL ARTICLE

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

