TREATMENT OF HUMAN MONOCYTE-DERIVED MACROPHAGES WITH A TNF-ALPHA SYNTHESIS INHIBITOR PRIOR TO HIV-1 INFECTION - CONSEQUENCES ON CYTOKINE PRODUCTION AND VIRAL REPLICATION

Human monocyte-derived macrophages (MDM) were infected with the viral strain HIV1/Ba-L and with the clinical isolates HIV1/DAS and HIV1/PAR. Kinetics of tumour necrosis factor alpha (TNF alpha) and interleukin- 6 (IL6) production were investigated for 28 days after infection. At t he early stages of infection we observed significant TNF alpha and IL6 secretion 2 to 10 h after infection, whatever the viral strain we use d. During the late events of MDM infection, TNF alpha and IL6 were det ected over 16 to 21 days following HIV1 infection, at the time of high viral replication. Pretreatment of MDM with a TNF alpha synthesis inh ibitor, RP 55778, 4 h prior to HIV infection induced a modified cytoki ne pattern during the first ten hours of infection: TNF alpha producti on was totally inhibited despite comparable amounts of IL6. At the lat e phases of the cell culture, a decrease in magnitude of both viral an d cytokine production as well as a delay in the appearance of reverse transcriptase activity and cytokine secretion peaks were observed in R P-55778-pretreated and HIV1-infected MDM cultures. Similar results wer e obtained after pretreatment of HIV1/DAS-infected MDM cultures with a n anti-TNF alpha monoclonal antibody.