Antagonistic Action of IFN-β and IFN-γ on High Affinity Fcγ Receptor Expression in Healthy Controls and Multiple Sclerosis Patients

Abstract

Monocyte-macrophage activation by IFN-γ is characterized by a pronounced increase of high affinity Fc receptors for IgG (FcγRI), capable of triggering respiratory burst, phagocytosis, Ab-dependent cytotoxicity, and release of proinflammatory cytokines. In view of the antagonism of IFN-β on IFN-γ action, of interest in the chronic inflammatory disorder multiple sclerosis, we examined the possible effect of IFN-β on IFN-γ induction of FcγRI gene expression. We found that IFN-β significantly down-regulated IFN-γ-induced FcγRI surface expression in peripheral blood monocytes from healthy donors, in a dose- and time-dependent manner. This down-regulation of FcγRI surface levels did not correspond to a decrease in FcγRI mRNA, suggesting a posttranscriptional effect of IFN-β. Down-regulation of FcγRI surface expression correlated with diminished cellular signaling through FcγRI, since the IFN-γ-induced increase in Fcγ receptor-triggered respiratory burst was nearly completely abrogated by simultaneous addition of IFN-β. Finally, the same antagonism between both IFNs on FcγRI surface expression was observed in peripheral blood monocytes derived from multiple sclerosis patients; inhibition by IFN-β was even increased (82 ± 11%), as compared with healthy controls (67 ± 4%). These results may partially help explain the beneficial effect of IFN-β in multiple sclerosis.