title: Glucocorticoid-induced immunoglobulin E synthesis by peripheral blood mononuclear cells from allergic and nonallergic subjects.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Budesonide-induced IgE generation in PBMCs differs in magnitude and seems to involve different mechanisms in atopic and non-atopic subjects.
authors.affiliation: Department of Immunology, Rheumatology and Allergy, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Chalubinski
authors.forename: Janina
authors.initials: J
authors.lastname: Grzegorczyk
authors.forename: Marek L
authors.initials: ML
authors.lastname: Kowalski
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D019819:Budesonide / Q000494:pharmacology; D023201:CD40 Ligand / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E; D019819:Budesonide