Antagonistic action of IFN-beta and IFN-gamma on high affinity Fc gamma receptor expression in healthy controls and multiple sclerosis patients.

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