Involvement of IL-6 in the anti-human immunodeficiency virus activity of IFN-τ in human macrophages

• Published in: International immunology 2005-08, Vol.17 (8), p.1047-1057
• Main Authors: Rogez-Kreuz, Christine, Manéglier, Benjamin, Martin, Marc, Dereuddre-Bosquet, Nathalie, Martal, Jacques, Dormont, Dominique, Clayette, Pascal
• Format: Article
• Language: English
• Subjects: 5′-OAS 2; 5′-oligoadenylate synthetase; Animals; anti-retroviral; GAPDH glyceraldehyde 3-phosphate dehydrogenase; HAS human serum albumin; HIV; HIV-1 - drug effects; HIV-1 - immunology; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; IDV indinavir; IFN; IFN-τ; IL-6; Immunologic Factors - pharmacology; immunomodulation; In Vitro Techniques; Interferon Type I - pharmacology; Interleukin-1 - biosynthesis; Interleukin-10 - biosynthesis; Interleukin-10 - pharmacology; Interleukin-6 - biosynthesis; Interleukin-6 - pharmacology; macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - virology; MIP macrophage inflammatory protein; neomycin; NIH National Institutes of Health; PKR serine–threonine kinase R; PMA phorbol myristate acetate; Pregnancy Proteins - pharmacology; PSN penicillin; Recombinant Proteins - pharmacology; RT reverse transcriptase; Sheep; streptomycin; TNF tumour necrosis factor; Tumor Necrosis Factor-alpha - biosynthesis; Virus Replication - drug effects
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxh285

IFN-τ is a non-cytotoxic type I IFN responsible for maternal recognition of the foetus in ruminants. IFN-τ has been found to inhibit HIV replication more strongly than human IFN-α, particularly in human monocyte-derived macrophages, without associated toxicity. Ovine IFN-τ uses the same anti-viral cellular pathways as human IFN-α in human macrophages, principally inhibiting the early steps of the biological cycle of HIV, preventing the integration of HIV DNA into the host-cell genome. In this study, we investigated the immunomodulatory properties of IFN-τ in human macrophages. We found that IFN-τ increased the production of IL-10 and IL-6, but not of IL-1β or tumour necrosis factor α, in unstimulated, LPS-stimulated and HIV-1/Ba-L-infected macrophages. We also found that treatment with IL-6 inhibited HIV replication. Moreover, the neutralization of IL-6 activity in the cell culture supernatants of IFN-τ-treated macrophages led to a decrease in the anti-retroviral effects of IFN-τ, suggesting that IL-6 was involved in the anti-viral activity induced by IFN-τ. By focusing on the very early steps of the biological cycle of HIV, we showed that IL-6 co-operated with IFN-τ to decrease intracellular HIV RNA levels 2 h after infection.