Corticosteroid inhibits IL-4 signaling through down-regulation of IL-4 receptor and STAT6 activity.

Corticosteroids are potent anti-inflammatory and immunosuppressive agents which down-regulate cytokine production and action. Yet, contradictory results have been reported for their effects on the interleukin (IL)-4-mediated response. Using type II Fc receptor for IgE/CD23 as a target gene, here we report that corticosteroids at 10(-4)-10(-6) M inhibit the IL-4 signaling pathway in human primary immune cells by down-regulation of the IL-4-induced IL-4 receptor expression and STAT6 activation. Although functional antagonism between steroid receptor and STAT6 for their transcriptional activity has been recently described, this is the first report that steroid inhibits the IL-4-induced STAT6 activity at the level of tyrosine phosphorylation and target DNA binding.