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International Immunology Advance Access published online on June 23, 2005
International Immunology, doi:10.1093/intimm/dxh285
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org
Received November 14, 2003
Accepted May 17, 2005

Article

Involvement of IL-6 in the anti-human immunodeficiency virus activity of IFN-{tau} in human macrophages

Christine Rogez-Kreuz 1, Benjamin Manéglier 2, Marc Martin 3, Nathalie Dereuddre-Bosquet 4, Jacques Martal 5, Dominique Dormont 3 *, and Pascal Clayette 4*

1 Service de Neurovirologie, Commissariat à l'Energie Atomique, Université Paris-Sud, CRSSA, EPHE, IPSC, Fontenay-aux-Roses, France; Unité de Biologie du Développement et de la Reproduction, Département de Physiologie Animale, Institut National de la Recherche Agronomique, Jouy-en-Josas, France
2 Service de Neurovirologie, Commissariat à l'Energie Atomique, Université Paris-Sud, CRSSA, EPHE, IPSC, Fontenay-aux-Roses, France; Unité de Pharmacologie, Département de Biologie, Centre Hospitalier de Versailles, Faculté de Médecine Paris Ile de France Ouest, Le Chesnay, France
3 Service de Neurovirologie, Commissariat à l'Energie Atomique, Université Paris-Sud, CRSSA, EPHE, IPSC, Fontenay-aux-Roses, France
4 SPI-BIO, CEA, 18, route du Panorama, B.P.6, 92265 Fontenay-aux-Roses Cedex, France
5 Unité de Biologie du Développement et de la Reproduction, Département de Physiologie Animale, Institut National de la Recherche Agronomique, Jouy-en-Josas, France

* To whom correspondence should be addressed.
Pascal Clayette, E-mail: pascal.clayette{at}cea.fr


  Abstract

IFN-{tau} is a non-cytotoxic type I IFN responsible for maternal recognition of the foetus in ruminants. IFN-{tau} has been found to inhibit HIV replication more strongly than human IFN-{alpha}, particularly in human monocyte-derived macrophages, without associated toxicity. Ovine IFN-{tau} uses the same anti-viral cellular pathways as human IFN-{alpha} 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-{tau} in human macrophages. We found that IFN-{tau} increased the production of IL-10 and IL-6, but not of IL-1{beta} or tumour necrosis factor {alpha}, 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-{tau}-treated macrophages led to a decrease in the anti-retroviral effects of IFN-{tau}, suggesting that IL-6 was involved in the anti-viral activity induced by IFN-{tau}. By focusing on the very early steps of the biological cycle of HIV, we showed that IL-6 co-operated with IFN-{tau} to decrease intracellular HIV RNA levels 2 h after infection.

Keywords: anti-retroviral; HIV; IFN; IFN-{tau}; IL-6; immunomodulation; macrophages.

*Dedicated to Professor Dominique Dormont who died in November 2003


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