Type I interferons are known to exhibit antiviral, antiproliferative and immunoregulatory activity, and are therefore an important tool in the host defense against infection by pathogens. Since the vessel lining endothelial cells constitute the link between tissue on the basal side and immune cells in blood on the apical side, they have an essential function in the immunological response to viral or bacterial infections. It is therefore of particular interest to gain more knowledge about IFN signaling and interferon regulated genes in ECs. In the course of this PhD-thesis, we investigated individual stimuli for their capacity to regulate IFN stimulated genes in primary endothelial cells. With respect to the natural diversity of IFN subtypes, we characterized the biological activity of 13 different IFN proteins on human ECs and fibroblasts. We investigated their effect in the regulation of ISGs, namely IFIT1, ISG15, CXCL10, CXCL11 and CCL8. The different IFN subtypes showed a remarkably consistent potency in ISG mRNA induction, independent of target gene and cellular background. We therefore classified IFN subtypes in three groups of high, intermediate and low activity. Furthermore, we gained evidence for cell type specific regulation of ISGs, as reflected in different levels of basal and IFN inducible ISG expression in endothelial cells versus fibroblasts. In comparison, we investigated ISG regulation in endothelial cells by cytokines other than type I interferon. Our results indicated that treatment of ECs with TNF, LPS or IL-1, directly induced transcript levels of IFIT1, ISG15 and CXCL10. Furthermore, we found antiviral effects of pro-inflammatory EC stimulation and assessed a possible contribution of autocrine IFN production. We gained evidence that autocrine IFN contributed to the sustained induction of ISG mRNA expression, but did not mediate the antiviral activity of pro-inflammatory cytokines.