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Cooperative inhibitory effects of budesonide and formoterol on eosinophil superoxide production stimulated by bronchial epithelial cell conditioned medium

Persdotter, Sofia; Lindahl, Maria; Malm-Erjefält, Monika LU ; von Wachenfeldt, Karin; Korn, Solange H.; Stevens, Tim and Miller-Larsson, Anna (2007) In International Archives of Allergy and Immunology 143(3). p.201-210
Abstract
Background: Improved asthma control by combinations of inhaled glucocorticosteroids (GCs) and long-acting beta(2)-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... (More)
Background: Improved asthma control by combinations of inhaled glucocorticosteroids (GCs) and long-acting beta(2)-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. Copyright (c) 2007 S. Karger AG, Basel (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
combination therapy, asthma, formoterol, bronchial epithelial cell, budesonide, superoxide, granulocyte macrophage colony, eosinophil, stimulating factor
in
International Archives of Allergy and Immunology
volume
143
issue
3
pages
201 - 210
publisher
Karger
external identifiers
  • wos:000246592800007
  • scopus:34250318594
ISSN
1423-0097
DOI
10.1159/000099463
language
English
LU publication?
yes
id
977e45a5-18c4-4209-b872-54bf04f86afd (old id 659516)
date added to LUP
2007-12-18 13:57:24
date last changed
2017-09-17 04:50:27
@article{977e45a5-18c4-4209-b872-54bf04f86afd,
  abstract     = {Background: Improved asthma control by combinations of inhaled glucocorticosteroids (GCs) and long-acting beta(2)-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 &lt; 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. Copyright (c) 2007 S. Karger AG, Basel},
  author       = {Persdotter, Sofia and Lindahl, Maria and Malm-Erjefält, Monika and von Wachenfeldt, Karin and Korn, Solange H. and Stevens, Tim and Miller-Larsson, Anna},
  issn         = {1423-0097},
  keyword      = {combination therapy,asthma,formoterol,bronchial epithelial cell,budesonide,superoxide,granulocyte macrophage colony,eosinophil,stimulating factor},
  language     = {eng},
  number       = {3},
  pages        = {201--210},
  publisher    = {Karger},
  series       = {International Archives of Allergy and Immunology},
  title        = {Cooperative inhibitory effects of budesonide and formoterol on eosinophil superoxide production stimulated by bronchial epithelial cell conditioned medium},
  url          = {http://dx.doi.org/10.1159/000099463},
  volume       = {143},
  year         = {2007},
}