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Differential anti-inflammatory effects of budesonide and a p38 MAPK inhibitor AZD7624 on COPD pulmonary cells

Authors Higham A, Karur P, Jackson N, Cunoosamy DM, Jansson P, Singh D

Received 15 December 2017

Accepted for publication 18 March 2018

Published 19 April 2018 Volume 2018:13 Pages 1279—1288

DOI https://doi.org/10.2147/COPD.S159936

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Charles Downs

Peer reviewer comments 2

Editor who approved publication: Dr Richard Russell


Andrew Higham,1,2 Pradeep Karur,1,2 Natalie Jackson,2 Danen M Cunoosamy,3 Paul Jansson,3 Dave Singh1,2

1Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, Manchester, UK; 2Medicines Evaluation Unit, The University Hospital of South Manchester, Manchester, UK; 3RIA IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden


Background: The effects of anti-inflammatory drugs in COPD patients may vary between different cell types. The aim of the current study was to assess the anti-inflammatory effects of the corticosteroid budesonide and a p38 MAPK inhibitor (AZD7624) on different cell types obtained from COPD patients and healthy controls.
Methods: Eight healthy smokers, 16 COPD infrequent exacerbators, and 16 frequent COPD exacerbators (≥2 exacerbations in the last year) were recruited for bronchoscopy and blood sampling. The anti-inflammatory effects of budesonide and AZD7624 were assessed on cytokine release from lipopolysaccharide-stimulated alveolar macrophages and peripheral blood mononuclear cells and polyinosinic:polycytidylic acid-stimulated bronchial epithelial cells.
Results: The anti-inflammatory effects of budesonide varied greatly within a patient according to the cell type studied. Bronchial epithelial cells showed the lowest sensitivity to budesonide, while peripheral blood mononuclear cells showed the greatest sensitivity. AZD7624 had a greater effect than budesonide on cytokine production from bronchial epithelial cells. Exacerbation frequency did not influence corticosteroid sensitivity.
Conclusion: We observed variable corticosteroid and p38 MAPK inhibitor anti-inflammatory responses within the same individual depending on the cell type studied. These findings support the use of multiple anti-inflammatory strategies in COPD patients due to differences between cell types.

Keywords: PBMC, corticosteroid, inflammation, exacerbation, macrophage, epithelial cell

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