Glucocorticoid-induced immunoglobulin E synthesis by peripheral blood mononuclear cells from allergic and nonallergic subjects

Abstract

Glucocorticoids (GCS) have been shown to induce IgE synthesis in human peripheral blood mononuclear cells (PBMCs) and purified B cells in vitro. However, the differences in immunoglobulin E (IgE) response to GCS between allergic and non-allergic individuals and the mechanism this interaction have not been elucidated. We aimed to compare the effect of GCS (budesonide) on interleukin (IL)-4-driven IgE production in vitro in allergic and non allergic subjects and assess the engagement of intracellular mechanisms. The study included 22 patients with allergic asthma and/or allergic rhinitis and 24 healthy volunteers. PBMCs were cultured for 11 days with IL-4 and budesonide and IgE concentrations in supernatants were assessed by immunoassays. T and B cell markers were assessed by flow cytometry. Budesonide enhanced IgE synthesis to higher extent in healthy donors than in allergic patients (mean increase of 16.5 vs 6.3 kU/L, P< .05 respectively) acting through glucocorticoid receptor. Budesonide significantly increased lymhoplasmocytoid cells percentage in both media-controlled (2.5-fold increase) and IL-4-stimulated PBMCs (2-fold increase). Added to IL-4 budesonide decreased the percentage of both T cells and CD40L(+) T cells, but strongly increased the percentage of B cells. Protein tyrosine kinase (PTK) inhibitor decreased, but NF-κB and protein kinase A (PKA) inhibitors expressed modulatory effects on budesonide-induced IgE synthesis. Budesonide-induced IgE generation in PBMCs differs in magnitude and seems to involve different mechanisms in atopic and non-atopic subjects.