Glucocorticoids increase the synthesis of immunoglobulin E by interleukin 4-stimulated human lymphocytes.

This study indicates that hydrocortisone (HC) markedly increases the synthesis ofimmunoglobulin E (IgE) by interleukin 4 (IL-4)-stimulated human lymphocytes. The effect is glucocorticoid specific and is obtained with low concentrations ofHC (0.1-10 uM). In both the early and the late phase of the IL-4induced response HC exerts its effects which are respectively IL4 dependent and IL-4 independent. The IgE potentiation cannot be explained by the inhibition of interferon--y (IFN-"y) production since it is observed in the absence of endogenous secretion of IFN-y. HC inhibits the production of IgE-binding factors (soluble CD23) and the expression of the low-affinity receptor for IgE, also known as the (FcERII) CD23 antigen; however, the residual expression of FcERII by IL4- and HCtreated peripheral blood mononuclear cells (PBMCs) is important since the IgE response of these cells is markedly inhibited by anti-CD23 monoclonal antibody. HC acts mainly by amplifying the cellular interactions between monocytes and lymphocytes; indeed, HC has no effect on monocyte-depleted PBMCs, and moreover, monocytes cannot be replaced by soluble factors. Most importantly, T cells are not required for the induction of IgE synthesis by costimulation with IL-4 and HC. However, the IgE response of rigorously T cell-depleted PBMCs may be further increased by the addition ofT cells. Further analysis of the permissive effect ofHC on the synthesis of IgE by T celldepleted PBMCs suggests thatHC acts in synergy with IL-4 to trigger the activation and the differentiation ofB cells into IgEproducing cells. (J. Clin. Invest. 1991. 87:870-877.) Key