Document 0161
 DOCN  M94A0161
 TI    Appraisal of potential therapeutic index of antioxidants on the basis of
       their in vitro effects on HIV replication in monocytes and interleukin
       2-induced lymphocyte proliferation.
 DT    9412
 AU    Aillet F; Gougerot-Pocidalo MA; Virelizier JL; Israel N; Unite
       d'Immunologie Virale, Institut Pasteur, Paris, France.
 SO    AIDS Res Hum Retroviruses. 1994 Apr;10(4):405-11. Unique Identifier :
       AIDSLINE MED/94347465
 AB    Antioxidant molecules have been suggested to be of therapeutic value in
       the treatment of HIV-infected patients. To evaluate this possibility, we
       examined in vitro the effects of two types of antioxidant molecules in
       terms of inhibition of HIV replication in monocytes, one of the main
       reservoirs of HIV, and also in terms of modulation of the immune
       competence as measured by PBMC proliferation. We tested the effects of
       BHA, a phenolic, lipid-soluble, chain-breaking antioxidant, and NAC, a
       known glutathione precursor with some direct free-radical scavenging
       properties as well, on the regulation of HIV-1 expression in latently
       infected U1 cells and in productively and chronically infected U937
       cells. Both antioxidants inhibited TNF- or PMA-induced NF-kappa B
       activity in U1 cells, as well as the sustained NF-kappa B activity
       permanently induced by the virus itself in chronically HIV-infected U937
       cells. This resulted in only a partial inhibition of TNF- or PMA-induced
       HIV replication in U1 cells, and no detectable effect on HIV replication
       in chronically infected U937 cells. This may be the first limitation to
       potential antiviral effects of antioxidant therapies. Another limitation
       is that antioxidant concentrations high enough to block NK-kappa B
       activation were shown to have a suppressive effect on immune functions
       in vitro, because NAC and BHA blocked IL-2-induced PBMC proliferation.
       These data warrant prudence in the design of antioxidant-based therapies
       aimed at suppressing HIV replication.
 DE    Acetylcysteine/PHARMACOLOGY  Antioxidants/ADMINISTRATION &
       DOSAGE/*PHARMACOLOGY  Base Sequence  Butylated
       Hydroxyanisole/PHARMACOLOGY  Cell Line  DNA, Viral/GENETICS  Human  HIV
       Infections/DRUG THERAPY  HIV-1/*DRUG EFFECTS/GENETICS/PHYSIOLOGY
       Interleukin-2/PHARMACOLOGY  Lymphocyte Transformation/DRUG EFFECTS
       Molecular Sequence Data  Monocytes/MICROBIOLOGY  NF-kappa B/METABOLISM
       Support, Non-U.S. Gov't  T4 Lymphocytes/MICROBIOLOGY  Virus
       Replication/*DRUG EFFECTS  JOURNAL ARTICLE

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