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

Abstract

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

Acknowledgments

This work was funded by AstraZeneca.

Disclosure

DMC and PJ are employees of AstraZeneca, which funded the study. DS has received sponsorship to attend international meetings, honoraria for lecturing or attending advisory boards, and research grants from various pharmaceutical companies including Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Genentech, GlaxoSmithKline, Glenmark, Johnson and Johnson, Merck, NAPP, Novartis, Pfizer, Skypharma, Takeda, Teva, Therevance, and Verona. The authors report no other conflicts of interest in this work.

Author contributions

All authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.