Document 3251
 DOCN  M94A3251
 TI    Cytokine production and viral replication in human MDMs treated with
       RP55778, a TNF alpha synthesis inhibitor, prior to HIV infection.
 DT    9412
 AU    Le Naour R; Henin Y; Raoul H; Bousseau A; Mabondzo A; Clayette P;
       Dormont D; IFRC, CEA, Fontenay aux Roses, France.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):119 (abstract no. PA0096). Unique
       Identifier : AIDSLINE ICA10/94369324
 AB    OBJECTIVES: To understand the relationships between HIV1 infection and
       cytokine secretion by using a TNF alpha synthesis inhibitor, RP55778.
       MATERIAL & METHODS: Human monocytes were isolated from peripheral blood
       mononuclear cells by counter current elutriation. Seven days after
       isolation, monocyte-derived macrophages (MDM) were treated 4 hours with
       RP55778 and then infected with the viral strain HIV1/Ba-L and with the
       clinical isolates HIV1/DAS, HIV1/PAR and HIV1/THI. Kinetics of both
       viral replication and TNF-alpha, IL6 and IL1 beta production were
       investigated during 28 days after infection. Cytokine secretion was
       investigated in HIV1 infected MDM culture supernatants using specific
       ELISA kit and viral replication was assessed by measuring RT activity.
       RESULTS: At the early stages of infection we observed a significant TNF
       alpha, IL6 and IL1 beta secretion 2 to 10 hours after infection. During
       the late events of MDM infection, TNF alpha and IL-6 were detected over
       16 to 21 days following HIV1 infection at the time of high viral
       replication. IL1 beta is not found at the same time points. Pretreatment
       of MDM with RP55778, 4 hours prior HIV infection induced a modified
       cytokine pattern during the 10 first hours of infection: TNF alpha
       production is inhibited despite comparable levels of IL6 and IL1 beta.
       At the late phases of viral infection, a decrease of magnitude of both
       viral and cytokine production as well as a delay in the appeareance of
       RT activity and cytokine secretion peaks was observed in RP55778
       pretreated and HIV1 infected MDM cultures. Similar results were obtained
       using anti-TNF alpha monoclonal antibody for pretreatment of HIV1
       infected MDM cultures. CONCLUSION: Our results demonstrate that in vitro
       HIV replication level in human MDM is partly depending upon the TNF
       alpha secretion taking place at the early time of infection.
 DE    Cells, Cultured  Cytokines/*BIOSYNTHESIS  Enzyme-Linked Immunosorbent
       Assay  Human  HIV-1/DRUG EFFECTS/*PHYSIOLOGY  Macrophages/DRUG
       EFFECTS/MICROBIOLOGY/*PHYSIOLOGY  Monocytes/DRUG
       EFFECTS/MICROBIOLOGY/*PHYSIOLOGY  Platelet Activating Factor/ANTAGONISTS
       & INHIB  Pyridines/*PHARMACOLOGY  Reverse
       Transcriptase/ANALYSIS/BIOSYNTHESIS  Thiazoles/*PHARMACOLOGY  Tumor
       Necrosis Factor/ANTAGONISTS & INHIB/*BIOSYNTHESIS  Virus
       Replication/*DRUG EFFECTS  MEETING ABSTRACT

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