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M94A3251.TXT
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1994-10-25
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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).