HIV-1 tat protein induces interleukin-10 production by human peripheral blood monocytes

In HIV-infected patients, production of IL-IO, a highly immunosuppressive cytokine, is associated with the progression of the disease towards AIDS. HIV-1 Tat, a protein secreted by infected cells and found free in the plasma of HIV-infected patients where it can interact with both infected and non-infected cells, could participate in this immune system disorder. In the present work, we show that Tat induces IL-IO production by peripheral blood monocytes of healthy donors in a dose and stimulation time-dependent manner. We show that the protein kinase C pathway plays an essential role in IL-10 production and exogenous Tat activates a potential substrate of PKC the trancriptionnal factor NFkB, that is required for IL-10 prodution,. Finally our results suggest that the effects of Tat are exerted at the membrane level.