Dexamethasone suppresses of IL-33-mediated mast cell activation in vitro and in vivo (HYP4P.314)

Abstract

Abstract Dexamethasone, a synthetic member of the glucocorticoid class of steroid drugs is known for its immunosuppressant and anti-inflammatory effects. Mast cells, critical effectors of allergic disease, can be activated by IL-33, a pro-inflammatory member of the IL-1 family. We found that Dexamethasone potently suppresses IL-33-stimulated cytokine secretion by mouse mast cells. We similarly found that Dexamethasone treatment in vivo reduced IL-33-mediated cytokine production and neutrophil infiltration in the murine peritoneum. We compared the activation status of signaling proteins during IL-33 stimulation, and found that Dexamethasone pretreatment significantly reduced Erk phosphorylation. However, we also observed that Dexamethasone-mediated suppression occurred when it was added simultaneously with IL-33, suggesting that inhibition occurrs even prior to Erk blockade. The effect of Dexamethasone on IL-33 stimulated NFkB-mediated gene transcription is currently under investigation. Our data show that Dexamethasone, a well-established therapy for inflammatory disease, can suppress IL-33-mediated mast cell activation, and may therefore be effective for treating diseases now being attributed to IL-33 effects.