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

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.