Comparison of fluticasone propionate and budesonide on COPD macrophage and neutrophil function
Authors Belchamber KBR, Thomas CMR, Dunne AE, Barnes PJ, Donnelly LE
Received 26 March 2018
Accepted for publication 16 May 2018
Published 17 September 2018 Volume 2018:13 Pages 2883—2897
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 2
Editor who approved publication: Dr Richard Russell
Kylie BR Belchamber, Catherine MR Thomas, Amy E Dunne, Peter J Barnes, Louise E Donnelly
Airway Disease Section, National Heart and Lung Institute, Dovehouse Street, Imperial College London, London, UK
Background: Inhaled corticosteroid use is associated with increased rates of pneumonia in COPD patients. The underlying mechanism is unknown, although recent data suggest that pneumonia is more frequent in patients treated with fluticasone propionate (FP) than budesonide. Macrophages and neutrophils from COPD patients are deficient in clearing bacteria, and this might explain increased bacterial colonization in COPD. Inhaled corticosteroid may further suppress this response; therefore, we examined the effect of FP and budesonide on phagocytosis of common respiratory pathogens by monocyte-derived macrophages (MDMs) and neutrophils.
Methods: MDMs from COPD patients (n=20–24) were preincubated with FP or budesonide for 1 or 18 hours, after which phagocytosis of fluorescently labeled inert beads or heat-killed Haemophilus influenzae/Streptococcus pneumoniae were measured fluorimetrically after 1 or 4 hours. Additionally, CXCL8, IL6, and TNFα concentrations in supernatants by ELISA, MDM-scavenger-receptor expression by flow cytometry, and MDM ability to kill bacteria were measured. Neutrophils from COPD patients (n=8) were preincubated with corticosteroids for 1 hour and bacteria phagocytosis measured by flow cytometry.
Results: After 1 hour’s preincubation, neither corticosteroid altered MDM phagocytosis of beads or H. influenzae; however, budesonide (10-7 M) increased S. pneumoniae phagocytosis by 23% (P<0.05). After 18 hours’ preincubation, neither corticosteroid altered MDM phagocytosis of any prey, although H. influenzae phagocytosis by budesonide was significantly greater compared to FP at 10-6 and 10-5 M (P<0.05). The 1-hour preincubation with either corticosteroid inhibited bacteria-induced CXCL8 release (at 10-7 and 10-5 M, P<0.05); however, this effect was lost at 18-hour preincubation. There was no change in receptor expression, bacterial killing, or neutrophil phagocytosis by either corticosteroid.
Conclusion: These data suggest that dissolved FP and budesonide do not have an overall effect on MDM or neutrophil phagocytosis of bacteria.
Keywords: COPD, macrophage, neutrophil, fluticasone propionate, budesonide
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