Interferons (IFN) represent a family of secreted glycoproteins with pleiotropic properties. These include a pronounced antiviral activity against a wide range of pathogenic viruses, a growth inhibitory effect on different tumor cells and immunomodulatory qualities during initiation and maintenance of specific host immune reactions. IFN-ƒÑ and IFN-£] - also referred to as type I IFN - are mainly induced by viral infections in a wide variety of different cell types. Following binding to specific cell surface receptors IFNs induce a multitude of different genes and establish an antiviral state in the target cells which results in limiting viral spread in the organism. Although in vitro nearly all cells are capable of generating an IFN-ƒÑ/ƒÒ response following viral infection, macrophages are considered the most important IFN producing cells. They are preferentially located near potential entry sites for pathogens and start IFN synthesis within 3-4 hours after contact with virus, well before other cells respond. Interestingly, this early production is caused by a positive feedback circuit which is known as "IFN Priming". It means that IFN can stimulate its own synthesis by inducing transcription factors that bind to specific regulatory regions of both IFN- and IFN-inducible genes. Macrophages constitutively secrete low amounts of IFN-£] that enables these cells to resist a viral attack and to mount a fast and vigorous IFN response. In our laboratory we are studying the molecular mechanism of IFN induction in macrophages. In addition we are focussing on genes induced by IFN in these cells. Our aim is to unravel some of the complexity of IFN actions and to define the individual contribution of IFN-induced genes on the diverse biological activities of IFN. Actually several new genes have been isolated that are induced by IFN-ƒÑ/£] and their biological role and genomic organisation are under study using functional assays, specific probes and monoclonal antibodies.