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 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.
Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, Manchester, UK. Andrew.Higham@manchester.ac.uk.
Andrew
A
Higham
Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, Manchester, UK. gbooth@meu.org.uk.
George
G
Booth
Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, Manchester, UK. Simon.Lea@manchester.ac.uk.
Simon
S
Lea
Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, Manchester, UK. tsouthworth@meu.org.uk.
Thomas
T
Southworth
Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, Manchester, UK. Jonathan.Plumb@manchester.ac.uk.
Jonathan
J
Plumb
Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, Manchester, UK. dsingh@meu.org.uk.
Dave
D
Singh
D000305:Adrenal Cortex Hormones / Q000494:pharmacology* / Q000627:therapeutic use*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism
D000305:Adrenal Cortex Hormones