Interferon-beta differentially regulates expression of the IL-12 family members p35, p40, p19 and EBI3 in activated human dendritic cells.

Interferon-beta is thought to provide clinical improvement to multiple sclerosis (MS) patients, in part, through its ability to suppress the generation of IL-12-dependent autoimmune T helper type 1 (Th1) cells by monocyte-derived dendritic cells (DC). We now describe how pre-incubation with 1000 U/ml of IFN-beta differentially regulates expression of multiple IL-12 family members in activated, immature human DC, inhibiting CD40/IFN-gamma-induced p35 and p40 message levels, while enhancing p19 and Epstein-Barr virus-induced gene 3 (EBI3) levels. IFN-beta-mediated inhibition of p40 mRNA and augmentation of p19 mRNA both require de novo protein synthesis. These findings indicate that IFN-beta will be found to have contrasting effects on DC secretion of the various IL-12 family homo- and heterodimers.