Budesonide, fluticasone propionate, and azithromycin do not modulate the membrane vesicle release by THP-1 macrophages and respiratory pathogens during macrophage infection

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.

Membrane Vesicle Production as a Bacterial Defense Against Stress

“…Only a limited number of studies have been allocated to the effect of these groups of antibiotics on changing membrane vesiculation patterns. The available results showed that they exert neither a significant inducing effect on membrane vesicle production nor on the level of virulence factors carried by membrane vesicles ( Bauwens et al, 2017 ; Volgers et al, 2017 ; Yun et al, 2018 ). In contrast to aminoglycosides, these groups of antibiotics do not directly affect membranes, and do not disrupt membrane stability.…”

Bacteria-derived extracellular vesicles: endogenous roles, therapeutic potentials and their biomimetics for the treatment and prevention of sepsis

“…Amelioration of systemic inflammatory response syndrome (SIRS) induced by OMV was observed through the administration of salbutamol and nortriptyline, which exhibited inhibitory effects on the release of IL-6 and tumor TNF from macrophages ( 161 ). The suppression of proinflammatory responses induced by EVs obtained from various bacterial species has been observed with the administration of budesonide, N-acetyl-L-cysteine, and fluticasone ( 162 , 163 ). Moreover, it has been demonstrated that ethyl pyruvate possesses the capability to impede various signaling pathways involved in the immune responses triggered by LPS and Escherichia coli OMV.…”

Inhibitors of Bacterial Extracellular Vesicles

“…Treatment of 0.1 μM 27 and 28 decreased TNF-α secretion by macrophages by approximately 84 and 83%, respectively in response to M. catarrhiae EVs. However, neither the release of EVs nor bacterial growth were affected ( Volgers et al, 2017b ). These findings suggest that 27 and 28 may have a positive effect on bacterial EV-induced inflammation, despite the observation that EV release and bacterial growth remained unaltered.…”