IFN-α induces anti-viral activity in P106-HLCs, which is accompanied by an immunometabolic switch. (a) P106-HLCs demonstrate strong innate immune activity upon stimulation with IFN-α. Stimulation with IFN-α induced ISG-expression (ISG15, Mx1) in a time-dependent manner, as determined by qPCR (N = 3). (b) Expression of CXCL10 protein upon IFN-α stimulation. Stimulation with IFN-α induced CXCL10 protein expression as determined by ELISA at the 24 h time point (N = 3). (c) Effect of innate immune activation on hepatocytes metabolic activity. Cells were stimulated with IFN-α for 16 h before CYP-activity and plasma protein production was measured and compared with unstimulated cells. The generation of an inflammatory environment as determined by upregulation of cytokines and chemokines was accompanied by the downregulation of plasma protein production (AFP, ALB) and (d) cytochrome P450 (CYP1A2, CYP3A) in order to redirect intracellular energy into defense strategies (N = 3). Results are shown as mean +/− SEM. * p < 0.05, ** p < 0.01, and *** p < 0.001. IFN = interferon, ISG = interferon stimulated genes, CXCL10 = C-X-C motif chemokine 10, AFP = alfa fetoprotein, ALB = albumin, CYP = cytochrome P450.