DEXAMETHASONE AND CYCLOSPORINE-A SUPPRESS MAST CELL-LEUKOCYTE CYTOKINE CASCADES BY MULTIPLE MECHANISMS

Based on in vitro findings with mouse mast cells and in vivo findings in mice, we report that dexamethasone or cyclosporin A can have at lea st three actions which interfere with the pathogenesis IgE-, mast-cell -, and cytoltine-dependent inflammatory reactions: suppression of the IgE-dependent increase in tumor necrosis factor (TNF)-alpha mRNA by ma st cells, inhibition of the IgE-dependent production of TNF-alpha prot ein by mast cells, and diminution of the responsiveness of target cell s to TNF-alpha. Our findings in mice raise the possibility that simila r actions of these agents in humans may account for some of the clinic al efficacy of corticosteroids and cyclosporin A in allergic diseases.