PMID- 21875545 OWN - NLM STAT- MEDLINE DCOM- 20111027 LR - 20110830 IS - 1534-4436 (Electronic) IS - 1081-1206 (Linking) VI - 107 IP - 3 DP - 2011 Sep TI - Glucocorticoid-induced immunoglobulin E synthesis by peripheral blood mononuclear cells from allergic and nonallergic subjects. PG - 251-7 LID - 10.1016/j.anai.2011.05.028 [doi] AB - 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-kappaB 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. CI - Copyright (c) 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. FAU - Chalubinski, Maciej AU - Chalubinski M AD - Department of Immunology, Rheumatology and Allergy, Faculty of Medicine, Medical University of Lodz, Lodz, Poland. FAU - Grzegorczyk, Janina AU - Grzegorczyk J FAU - Kowalski, Marek L AU - Kowalski ML LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110722 PL - United States TA - Ann Allergy Asthma Immunol JT - Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology JID - 9503580 RN - 0 (Glucocorticoids) RN - 0 (NF-kappa B) RN - 0 (Protein Kinase Inhibitors) RN - 147205-72-9 (CD40 Ligand) RN - 207137-56-2 (Interleukin-4) RN - 37341-29-0 (Immunoglobulin E) RN - 51333-22-3 (Budesonide) SB - IM MH - Adult MH - Asthma/*immunology MH - B-Lymphocytes/drug effects/immunology MH - Budesonide/pharmacology MH - CD40 Ligand/immunology MH - Female MH - Glucocorticoids/*pharmacology MH - Humans MH - Hypersensitivity/*immunology MH - Immunoglobulin E/*biosynthesis MH - Interleukin-4/immunology MH - Leukocytes, Mononuclear/*drug effects/immunology MH - Male MH - Middle Aged MH - NF-kappa B/antagonists & inhibitors/immunology MH - Protein Kinase Inhibitors/pharmacology MH - Rhinitis, Allergic, Perennial/*immunology MH - T-Lymphocytes/drug effects/immunology MH - Young Adult EDAT- 2011/08/31 06:00 MHDA- 2011/10/28 06:00 CRDT- 2011/08/31 06:00 PHST- 2011/02/01 00:00 [received] PHST- 2011/05/24 00:00 [revised] PHST- 2011/05/31 00:00 [accepted] PHST- 2011/08/31 06:00 [entrez] PHST- 2011/08/31 06:00 [pubmed] PHST- 2011/10/28 06:00 [medline] AID - S1081-1206(11)00420-0 [pii] AID - 10.1016/j.anai.2011.05.028 [doi] PST - ppublish SO - Ann Allergy Asthma Immunol. 2011 Sep;107(3):251-7. doi: 10.1016/j.anai.2011.05.028. Epub 2011 Jul 22.