Budesonide, fluticasone propionate, and azithromycin do not modulate the membrane vesicle release by THP-1
Charlotte Volgers1, Gert E Grauls1, Pauline H M Hellebrand1
1Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre, P. Debyelaan 25, 6229 HZ, Maastricht, The Netherlands.
Abstract:
Patients with more severe chronic obstructive pulmonary disease frequently experience exacerbations and it is estimated that up to 50% of these exacerbations are associated with bacterial infections. The mainstay treatment for these infection-related exacerbations constitutes the administration of glucocorticoids, alone or in combination with antibiotics. A recent line of evidence demonstrates that many hormones including the steroid beclomethasone can also directly affect bacterial growth, virulence, and antibiotic resistance. The effect of these regimens on the release of potentially virulent and toxic membrane vesicles (MVs) is at present unclear. In this study, we determined the effect of several pharmacological agents on MVs release by and bacterial growth of common respiratory pathogens. We found that neither the release of MVs nor the bacterial growth was affected by the glucocorticoids budesonide and fluticasone. The macrolide antibiotic azithromycin only inhibited the growth of Moraxella catarrhalis but no effects were observed on bacterial MV release at a concentration that is achieved locally in the epithelial lining on administration. The macrophage pro-inflammatory response to MVs was significantly reduced after treatment with budesonide and fluticasone but not by azithromycin treatment. Our findings suggest that these glucocorticoids may have a positive effect on infection-related inflammation although the bacterial growth and MV release remained unaffected.
Insights
Glucocorticoids like budesonide and fluticasone did not affect bacterial growth or membrane vesicle release in COPD pathogens. However, these steroids reduced the inflammatory response to membrane vesicles.
Area of Science:
- Respiratory Medicine
- Microbiology
- Pharmacology
Background:
- Chronic obstructive pulmonary disease (COPD) exacerbations are often linked to bacterial infections.
- Current treatments include glucocorticoids and antibiotics.
- Glucocorticoids may directly impact bacterial properties, but their effect on bacterial membrane vesicle (MV) release is unknown.
Purpose of the Study:
- To investigate the impact of glucocorticoids and azithromycin on bacterial growth and MV release.
- To assess the effect of these agents on the macrophage pro-inflammatory response to MVs.
Main Methods:
- Exposure of common respiratory pathogens to budesonide, fluticasone, and azithromycin.
- Measurement of bacterial growth and MV release.
- Assessment of macrophage inflammatory response to MVs after pharmacological treatment.
Main Results:
- Budesonide and fluticasone did not alter bacterial growth or MV release.
- Azithromycin inhibited Moraxella catarrhalis growth but did not affect MV release.
- Glucocorticoid treatment significantly reduced macrophage pro-inflammatory response to MVs, while azithromycin did not.
Conclusions:
- Glucocorticoids may mitigate infection-related inflammation in COPD by modulating the host response to MVs.
- Bacterial growth and MV release are not directly inhibited by commonly used glucocorticoids or azithromycin at relevant concentrations.
