Dexamethasone and cyclosporin 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 least three actions which interfere with the pathogenesis IgE-, mast-cell-, and cytokine-dependent inflammatory reactions: suppression of the IgE-dependent increase in tumor necrosis factor (TNF)-alpha mRNA by mast cells, inhibition of the IgE-dependent production of TNF-alpha protein by mast cells, and diminution of the responsiveness of target cells to TNF-alpha. Our findings in mice raise the possibility that similar actions of these agents in humans may account for some of the clinical efficacy of corticosteroids and cyclosporin A in allergic diseases.