Interleukin (IL)-10 has potent activity against HIV in vitro, and we have identified two mechanisms of action. One mechanism involves the inhibition of inflammatory mediators, such as IL-1, IL-6, and tumor necrosis factor (TNF), which are potent inducers of HIV replication. The second mechanism of HIV inhibition by IL-10 is related to a block in cellular activation and replication. A phase I clinical trial was undertaken to study the effect of IL-10 in HIV-infected individuals. We studied: 1) HIV-uninfected subjects receiving 25 microg/kg IL-10 intravenously (iv), 2) HIV-infected subjects with CD4+ T-cell counts less than 200, 3) between 200 and 500, and 4) over 500 cells per microliter receiving IL-10 at 1, 10, and 25 microg/kg iv, and 5) HIV-infected subjects with CD4+ T-cell counts above 200 per (L receiving 1, 10, 25 microg/kg of IL-10 subcutaneously. The HIV-uninfected subjects were studied for the ability of HIV to replicate in their cells pre and post IL-10, while The HIV+ subjects were followed for alterations in viral load. All subjects were analyzed for IL-10 induced changes in cytokine secretion profiles. After a single administration of IL-10, the peripheral blood cells of uninfected subjects were less able to support viral growth when exposed to HIV in vitro for up to 24 hours after the IL-10 treatment. TNF secretion from peripheral blood mononuclear cells (PBMCs) was also inhibited in response to in vitro LPS stimulation after IL-10 administration in vivo. Plasma viral loads in HIV-infected subjects transiently decreased (average of 70%) after IL-10 with a peak decrease at 6 to 12 hours post IL-10 infusion. IL-10 was well tolerated with no serious adverse events. Current studies are attempting to identify the mechanisms of HIV inhibition in vivo. The phase I clinical trial will be continued and a phase 2 multi-dose study is being designed.
| Sarkar, Srijata; Han, Junfeng; Sinsimer, Kristina S et al. (2011) RNA-binding protein AUF1 regulates lipopolysaccharide-induced IL10 expression by activating IkappaB kinase complex in monocytes. Mol Cell Biol 31:602-15 |
