Interferon alfa (IFN-α) is an approved therapeutic agent for chronic hepatitis C. To directly characterize the effects of IFN-α in humans, we used microarrays to profile gene expression in peripheral blood mononuclear cells (PBMCs) from hepatitis C patients treated with IFN-α. Seven patients were studied using two strategies: (1) in vivo: PBMCs were collected immediately before the first dose of IFN-α, and 3 and 6 hours after the dose; (2) ex vivo: PBMCs that were collected before the first IFN-α dose were incubated with IFN-α for 3 and 6 hours. The microarray datasets were analyzed with significance analysis of microarrays (SAM) to identify genes regulated by IFN-α. We identified 516 named genes up-regulated at least 2-fold, at a false discovery rate (FDR) of less than 1%. In vivo and ex vivo studies generated similar results. No genes were identified as regulated differently between these 2 experimental conditions. The up-regulated genes belonged to a broad range of functional pathways and included multiple genes thought to be involved in the direct antiviral effect of IFN-α. Of particular interest, 88 genes directly relating to functions of immune cells were up-regulated, including genes involved in antigen processing and presentation, T-cell activation, lymphocyte trafficking, and effector functions, suggesting that IFN-α up-regulates multiple genes involving different aspects of immune responses to enhance immunity against hepatitis C virus. In conclusion, IFN-α-inducible genes can be identified in human PBMCs in vivo as well as ex vivo. Signature changes associated with diffeferent treatment outcomes may be found among these genes.
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