Anti-inflammatory action of type I interferons deduced from mice expressing interferon beta

Type I interferons (IFN) are widely used for the therapeutic treatment of v iral infections, tumor growth and various chronic diseases such as multiple sclerosis. Antagonism between type I IFNs and IFN-gamma has been described in cells of the immune system, in particular in the activation of macropha ges. To study the systemic effects of type I IFNs we used transgenic mice c arrying a human IFN-beta (hIFN-beta) gene under the control of the rat insu lin I promoter. These animals expressed high levels of hIFN-beta in beta-pa ncreatic cells, and the ability of the macrophages to respond to proinflamm atory stimuli was analyzed. Transgenic mice exhibited an increased extravas ation of cells to the peritoneal cavity after eliciting with thioglycollate broth. The expression of the inducible form of nitric oxide synthase and c yclooxygenase-2, two enzymes involved in inflammation, was impaired in tran sgenic animals challenged with lipopolysaccharide and IFN-gamma. Analysis o f the mechanisms leading to this attenuated inflammatory response showed a decrease in the serum levels of TNF-alpha and an inhibition of the activati on of the transcription factor NF-kappa B in various tissues. These results indicate that systemic administration of IFN-beta might influence the resp onse to pro-inflammatory stimuli, in particular through the antagonism of I FN-gamma signaling.