Abstract
BackgroundAirway inflammation is a key feature of chronic obstructive pulmonary disease (COPD) and inhaled corticosteroids (ICS) remain the main treatment for airway inflammation. Studies have noted the increased efficacy of ICS and long-acting beta 2 agonist (LABA) combination therapy in controlling exacerbations and improving airway inflammation than either monotherapy. Further studies have suggested that LABAs may have inherent anti-inflammatory potential, but this has not been well-studied.ObjectiveWe hypothesize that the LABA olodaterol can inhibit airway inflammation resulting from exposure to respiratory syncytial virus (RSV) via its binding receptor, the β2-adrenergic receptor.MethodsHuman bronchial epithelial brushing from patients with and without COPD were cultured into air–liquid interface (ALI) cultures and treated with or without olodaterol and RSV infection to examine the effect on markers of inflammation including interleukin-8 (IL-8) and mucus secretion. The cell line NCI-H292 was utilized for gene silencing of the β2-adrenergic receptor via siRNA as well as receptor blocking via ICI 118,551 and butaxamine.ResultsAt baseline, COPD-ALIs produced greater amounts of IL-8 than control ALIs. Olodaterol reduced RSV-mediated IL-8 secretion in both COPD and control ALIs and also significantly reduced Muc5AC staining in COPD-ALIs infected with RSV. A non-significant reduction was seen in control ALIs. Gene silencing of the β2-adrenergic receptor in NCI-H292 negated the ability of olodaterol to inhibit IL-8 secretion from both RSV infection and lipopolysaccharide stimulus, as did blocking of the receptor with ICI 118,551 and butaxamine.ConclusionsOlodaterol exhibits inherent anti-inflammatory properties on the airway epithelium, in addition to its bronchodilation properties, that is mediated through the β2-adrenergic receptor and independent of ICS usage.
Highlights
Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition that is characterized by persistent airflow limitation and is a major cause of morbidity and mortality worldwide [1, 2]
Human bronchial epithelial brushing from patients with and without chronic obstructive pulmonary disease (COPD) were cultured into air–liquid interface (ALI) cultures and treated with or without olodaterol and respiratory syncytial virus (RSV) infection to examine the effect on markers of inflammation including interleukin-8 (IL-8) and mucus secretion
Olodaterol reduced RSVmediated IL-8 secretion in both COPD and control ALIs and significantly reduced mucin 5AC (Muc5AC) staining in COPD-ALIs infected with RSV
Summary
Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition that is characterized by persistent airflow limitation and is a major cause of morbidity and mortality worldwide [1, 2]. First approved in 2013, olodaterol (Striverdi “Respimat”) is a novel inhaled ultra-LABA with over 24 h of bronchodilatory effect [2, 10,11,12]. It is a potent and selective β2-adrenergic receptor (β2AR) agonist with a rapid onset of action [8, 9, 13]. We hypothesize that LABAs have their own intrinsic antiinflammatory effects when applied to the airways of COPD patients via the airway epithelium. Airway inflammation is a key feature of chronic obstructive pulmonary disease (COPD) and inhaled corticosteroids (ICS) remain the main treatment for airway inflammation. Further studies have suggested that LABAs may have inherent anti-inflammatory potential, but this has not been well-studied
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