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The effects of corticosteroids on COPD lung macrophages: a pooled analysis

BACKGROUND: There is large variation in the therapeutic response to inhaled corticosteroids (ICS) in COPD patients. We present a pooled analysis of our previous studies investigating the effects of corticosteroids on lung macrophages, in order to robustly determine whether corticosteroid sensitivity...

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Autores principales: Higham, Andrew, Booth, George, Lea, Simon, Southworth, Thomas, Plumb, Jonathan, Singh, Dave
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545868/
https://www.ncbi.nlm.nih.gov/pubmed/26289362
http://dx.doi.org/10.1186/s12931-015-0260-0
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author Higham, Andrew
Booth, George
Lea, Simon
Southworth, Thomas
Plumb, Jonathan
Singh, Dave
author_facet Higham, Andrew
Booth, George
Lea, Simon
Southworth, Thomas
Plumb, Jonathan
Singh, Dave
author_sort Higham, Andrew
collection PubMed
description BACKGROUND: There is large variation in the therapeutic response to inhaled corticosteroids (ICS) in COPD patients. We present a pooled analysis of our previous studies investigating the effects of corticosteroids on lung macrophages, in order to robustly determine whether corticosteroid sensitivity in COPD cells is reduced compared to controls, and also to evaluate the degree of between individual variation in drug response. METHODS: Data from 20 never smokers (NS), 27 smokers (S) and 45 COPD patients was used. Lung macropahges had been stimulated with lipopolysaccharide (LPS), with or without the corticosteroid dexamethasone, and tumour necrosis factor (TNF)-α, interleukin (IL)-6 and chemokine C-X-C motif ligand (CXCL) 8 production was measured. RESULTS: There was no difference in the anti-inflammatory effects of corticosteroids when comparing group mean data of COPD patients versus controls. The inhibition of TNF-α and IL-6 was greater than CXCL8. The effects of corticosteroids varied considerably between subjects, particularly at lower corticosteroid concentrations. CONCLUSIONS: We confirm that overall corticosteroid sensitivity in COPD lung macrophages is not reduced compared to controls. The varied effect of corticosteroids between subjects suggests that some individuals have an inherently poor corticosteroid response. The limited suppression of lung macrophage derived CXCL8 may promote neutrophilic inflammation in COPD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-015-0260-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-45458682015-08-23 The effects of corticosteroids on COPD lung macrophages: a pooled analysis Higham, Andrew Booth, George Lea, Simon Southworth, Thomas Plumb, Jonathan Singh, Dave Respir Res Research BACKGROUND: There is large variation in the therapeutic response to inhaled corticosteroids (ICS) in COPD patients. We present a pooled analysis of our previous studies investigating the effects of corticosteroids on lung macrophages, in order to robustly determine whether corticosteroid sensitivity in COPD cells is reduced compared to controls, and also to evaluate the degree of between individual variation in drug response. METHODS: Data from 20 never smokers (NS), 27 smokers (S) and 45 COPD patients was used. Lung macropahges had been stimulated with lipopolysaccharide (LPS), with or without the corticosteroid dexamethasone, and tumour necrosis factor (TNF)-α, interleukin (IL)-6 and chemokine C-X-C motif ligand (CXCL) 8 production was measured. RESULTS: There was no difference in the anti-inflammatory effects of corticosteroids when comparing group mean data of COPD patients versus controls. The inhibition of TNF-α and IL-6 was greater than CXCL8. The effects of corticosteroids varied considerably between subjects, particularly at lower corticosteroid concentrations. CONCLUSIONS: We confirm that overall corticosteroid sensitivity in COPD lung macrophages is not reduced compared to controls. The varied effect of corticosteroids between subjects suggests that some individuals have an inherently poor corticosteroid response. The limited suppression of lung macrophage derived CXCL8 may promote neutrophilic inflammation in COPD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-015-0260-0) contains supplementary material, which is available to authorized users. BioMed Central 2015-08-20 2015 /pmc/articles/PMC4545868/ /pubmed/26289362 http://dx.doi.org/10.1186/s12931-015-0260-0 Text en © Higham et al. 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Higham, Andrew
Booth, George
Lea, Simon
Southworth, Thomas
Plumb, Jonathan
Singh, Dave
The effects of corticosteroids on COPD lung macrophages: a pooled analysis
title The effects of corticosteroids on COPD lung macrophages: a pooled analysis
title_full The effects of corticosteroids on COPD lung macrophages: a pooled analysis
title_fullStr The effects of corticosteroids on COPD lung macrophages: a pooled analysis
title_full_unstemmed The effects of corticosteroids on COPD lung macrophages: a pooled analysis
title_short The effects of corticosteroids on COPD lung macrophages: a pooled analysis
title_sort effects of corticosteroids on copd lung macrophages: a pooled analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545868/
https://www.ncbi.nlm.nih.gov/pubmed/26289362
http://dx.doi.org/10.1186/s12931-015-0260-0
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