AEGiS-07IAC: Effects of AZT and ddI on TNF alpha and IL6 production.

7th International AIDS Conference


Florence, Italy — June 16-21, 1991

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Effects of AZT and ddI on TNF alpha and IL6 production.

Int Conf AIDS 1991 Jun 16-21; 7:215 (abstract no. W.B.2135)
Goujard C, Delfraissy JF, Wallon C, Boue F, Galanaud P; Service de Medecine Interne and INSERM U 131, Hopital A.Beclere-Clamart-92140-France

OBJECTIVE: AZT and ddI penetrate human monocytes and interfere with reverse transcriptase activity in infected cells. However little is known on the consequences of these drugs on monocyte functions. We investigate the effects of AZT and ddI on TNF and IL6 production. Both cytokines are elevated in HIV patients and can enhance HIV replication.

METHODS: In vitro: monocytes from normal subjects and HIV patients were cultured in the presence of different drug concentrations (0,25 to 10 mu mol). Spontaneous, LPS and HIV induced cytokines production was tested in culture supernatants from 24 to 72 hours. IL6 was measured by a functional assay (Bg cell line), IL6 and TNF by ELISA. In vivo: IL6 and TNF serum levels, and spontaneous monocytes production were studied in patients (AZT: n=10, ddI: n=8) before and after drug therapy (months 0, 1, 3).

RESULTS: AZT nor ddI do not inhibit in vitro IL6 and TNF production by normal monocytes (spontaneous, LPS or HIV induced). Monocytes from HIV patients exhibit higher cytokines production which is unmodified by drug addition. In contrast after in vivo drug therapy IL6 and TNF serum levels are significantly decreased as well as spontaneous cytokines production by HIV infected monocytes.

CONCLUSIONS: AZT and ddI do not interfere with in vitro IL6 and TNF production. However they can negatively regulate in vivo secretion of both cytokines. This later effect is probably due to the inhibition of viral replication, and may be relevant for the beneficial effect of the drug in HIV infection.

Keywords: AEGIS, Didanosine, Zidovudine, Interleukin-6, Tumor Necrosis Factor, Monocytes, HIV Infections, Lipopolysaccharides, RNA-Directed DNA Polymerase, Anti-HIV Agents, Reverse Transcriptase Inhibitors, Virus Replication, Human, In Vitro, virology, ICA7KWDaegis,didanosine,zidovudine,interleukin-6,tumornecrosisfactor,monocytes,hivinfections,lipopolysaccharides,rna-directeddnapolymerase,anti-hivagents,reversetranscriptaseinhibitors,virusreplication,human,invitro,virology,ica7
910616
WB2135

Copyright © 1991 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.