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 pron ounced increase of high affinity Fc receptors for Ige (Fc gamma RI), c apable of triggering respiratory burst, phagocytosis, Ab-dependent cyt otoxicity, and release of proinflammatory cytokines, In view of the an tagonism of IFN-beta on IFN-gamma action, of interest in the chronic i nflammatory disorder multiple sclerosis, we examined the possible effe ct 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 heal thy 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 g amma RI mRNA, suggesting a posttranscriptional effect of IFN-beta. Dow n-regulation of Fc gamma RI surface expression correlated with diminis hed cellular signaling through Fc gamma RI, since the IFN-gamma-induce d increase in Fc gamma receptor-triggered respiratory burst was nearly completely abrogated by simultaneous addition of IFN-beta. Finally, t he same antagonism between both IFNs on Fc gamma RI surface expression was observed in peripheral blood monocytes derived from multiple scle rosis patients; inhibition by IFN-beta was even increased (82 +/- 11%) , as compared with healthy controls (67 +/- 4%). These results may par tially help explain the beneficial effect of IFN-beta in multiple scle rosis.