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Table of Contents
Vol. 143, No. 3, 2007
Issue release date: June 2007
Section title: Original Paper
Int Arch Allergy Immunol 2007;143:201–210
(DOI:10.1159/000099463)

Cooperative Inhibitory Effects of Budesonide and Formoterol on Eosinophil Superoxide Production Stimulated by Bronchial Epithelial Cell Conditioned Medium

Persdotter S.a · Lindahl M.a · Malm-Erjefält M.b · von Wachenfeldt K.a · Korn S.H.a · Stevens T.a · Miller-Larsson A.a
aAstraZeneca R&D Lund and bDepartment of Clinical and Experimental Pharmacology, Lund University Hospital, University of Lund, Lund, Sweden

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: December 12, 2005
Accepted: November 20, 2006
Published online: February 09, 2007
Issue release date: June 2007

Number of Print Pages: 10
Number of Figures: 6
Number of Tables: 1

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA

Abstract

Background: Improved asthma control by combinations of inhaled glucocorticosteroids (GCs) and long-acting β2-agonists (LABAs) includes a reduced frequency and severity of exacerbations. In view of the association of exacerbations with increased airway inflammation, the question has arisen as to whether LABAs are able to complement the known anti-inflammatory activity of GCs. To address this, we studied the effects of a LABA, formoterol (FORM), and a GC, budesonide (BUD), alone and in combination, on bronchial epithelial cell-mediated eosinophil superoxide production in vitro.Methods: We employed 2 experimental approaches. First, superoxide production by human eosinophils incubated with conditioned medium (CM) from human bronchial epithelial cells cultured for 24 h with vehicle, BUD, FORM or BUD + FORM was measured (Epi/Eos assay). Second, eosinophils were stimulated with vehicle-CM to which the drugs were added (Eos assay). Superoxide production was determined as the superoxide dismutase-inhibitable reduction of ferricytochrome C. Results: CM increased eosinophil superoxide generation (p < 0.01) and epithelial-derived granulocyte macrophage colony-stimulating factor was the mediator responsible. In both assays, FORM dose-dependently inhibited eosinophil superoxide similarly and in the same concentration range as BUD. The BUD + FORM combination was more effective than BUD alone, and it completely inhibited CM-induced superoxide production in the Epi/Eos assay, suggesting complementary effects of both drugs on bronchial epithelial cells and eosinophils. Conclusions: The cooperative, inhibitory effects of BUD and FORM on eosinophils and bronchial epithelial cells, in terms of their effects on eosinophil superoxide production, may represent a possible mechanism for the enhanced anti-inflammatory efficacy of BUD and FORM combination therapy of asthma.

© 2007 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: December 12, 2005
Accepted: November 20, 2006
Published online: February 09, 2007
Issue release date: June 2007

Number of Print Pages: 10
Number of Figures: 6
Number of Tables: 1

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA


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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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