INDUCTION OF INTERLEUKIN-4 AND INTERLEUKIN-5 EXPRESSION IN MAST-CELLSIS INHIBITED BY GLUCOCORTICOIDS

Inflammation in asthma and other allergic diseases is characterized by excessive production of immunoglobulin E (IgE) and the influx of leuk ocytes, especially eosinophils, Interleukin 1 (IL-4) and IL-5 are esse ntial for IgE production and eosinophilia, respectively, and are produ ced by mast cells in allergic conditions, for which glucocorticoids ar e widely used therapeutically. We assessed the effect of glucocorticoi ds on IL-4 and IL-5 mRNA production by the RBL-2H3 cell line, an analo g of mucosal mast cells, IL-4 and IL-5 mRNAs were induced by an antige n that is used to cross-link receptor bound IgE, by calcium ionophore, or by ionophore with phorbol ester and were markedly inhibited by dex amethasone, In cells activated with ionophore and phorbol ester, 10(-6 ) M dexamethasone reduced the IL-4 and IL-5 mRNA levels to only 12.8 a nd 5.7%, respectively, of those in cells without dexamethasone, and 10 (-9) M dexamethasone caused reductions to 27 and 56%, respec tively, H ydrocortisone at 10(-6) and 10(-7) M almost completely inhibited IL-4 and IL-5 mRNA production, Dexamethasone was markedly inhibitory even i f it was added after the cells were activated, provided that it was pr esent in the cultures for at least 1.5 h, These studies indicate that the expression of IL-4 and IL-5 mRNAs by mast cells is highly sensitiv e to glucocorticoids. The data suggest that these inhibitory effects m ay contribute to the clinical efficacy of glucocorticoids in the thera py of allergic diseases.