Document 2544
 DOCN  M94A2544
 TI    Suppression of HIV replication by the interleukin-1 receptor antagonist.
 DT    9412
 AU    Poli G; Kinter AL; Fox LM; Turchetto L; Vicenzi E; Fauci AS; San
       Raffaele Institute, Milano, Italy.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):28 (abstract no. 087A). Unique
       Identifier : AIDSLINE ICA10/94370031
 AB    OBJECTIVE: To investigate the potential role of the natural antagonist
       of interleukin-1 (IL-1) receptor (IL-1ra), on cells infected with the
       human immunodeficiency virus (HIV). METHODS: Peripheral blood
       mononuclear cells (PBMC) of HIV seronegative donors were maintained in
       culture with medium enriched of IL-2 and infected with different
       laboratory-adapted and primary isolates of HIV type-1 in the presence or
       absence of different concentrations of IL-1ra. The chronically infected
       promonocytic cell line U1, a previously described model of HIV latency
       and induction of viral expression, was stimulated by different
       cytokines, including IL-1 alpha and IL-1 beta, in the presence or
       absence of different concentrations of IL-1ra. HIV production was
       monitored by reverse transcriptase (RT) activity. RESULTS: IL-1ra
       suppressed consistently HIV replication in several cultures of PBMC
       maintained in IL-2-enriched medium, as determined by the levels of RT
       activity measured in the culture supernatants. Similar effects were
       obtained with both anti-IL-1 beta, but not anti-IL-1 alpha, antibodies
       (Ab) and with Ab directed to the type I, but not the type II, IL-1
       receptor. In addition, IL-1ra blocked the induction of HIV expression in
       U1 cells stimulated with either IL-1 alpha or IL-1 beta, but did not
       interfere with the stimulatory activity of cytokines other than IL-1,
       including tumor necrosis factor alpha and IL-6. DISCUSSION AND
       CONCLUSIONS: IL-1 induces HIV replication in vitro. IL-1ra, whose only
       known function is the inhibition of IL-1 signal transduction via binding
       of the cytokine receptors, exerts suppressive effects on HIV replication
       derived by endogenously secreted IL-1 (as in the case of IL-2-stimulated
       PBMC) or virus expression induced by exogenously added IL-1 (as seen in
       U1 cells). These in vitro studies serve as the basis for the formulation
       of novel therapeutic strategies aimed at limiting the spreading of the
       virus in vivo by blocking the production or effects of HIV-inductive
       cytokines, such as IL-1.
 DE    Cells, Cultured  Cytokines/PHARMACOLOGY  Human  HIV-1/*DRUG
       EFFECTS/PHYSIOLOGY  Interleukin-1/*PHARMACOLOGY  Recombinant
       Proteins/PHARMACOLOGY  Reverse Transcriptase/METABOLISM
       Sialoglycoproteins/*PHARMACOLOGY  Virus Replication/*DRUG EFFECTS
       MEETING ABSTRACT

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