The long‐acting β₂‐adrenoceptor agonist olodaterol attenuates pulmonary inflammation

Abstract

Background and Purposeβ2-adrenoceptor agonists are widely used in the management of obstructive airway diseases. Besides their bronchodilatory effect, several studies suggest inhibitory effects on various aspects of inflammation. The aim of our study was to determine the efficacy of the long-acting β2-adrenoceptor agonist olodaterol to inhibit pulmonary inflammation and to elucidate mechanism(s) underlying its anti-inflammatory actions.Experimental ApproachOlodaterol was tested in murine and guinea pig models of cigarette smoke- and LPS-induced lung inflammation. Furthermore, effects of olodaterol on the LPS-induced pro-inflammatory mediator release from human parenchymal explants, CD11b adhesion molecule expression on human granulocytes TNF-α release from human whole blood and on the IL-8-induced migration of human peripheral blood neutrophils were investigated.Key ResultsOlodaterol dose-dependently attenuated cell influx and pro-inflammatory mediator release in murine and guinea pig models of pulmonary inflammation. These anti-inflammatory effects were observed at doses relevant to their bronchodilatory efficacy. Mechanistically, olodaterol attenuated pro-inflammatory mediator release from human parenchymal explants and whole blood and reduced expression of CD11b adhesion molecules on granulocytes, but without direct effects on IL-8-induced neutrophil transwell migration.Conclusions and ImplicationsThis is the first evidence for the anti-inflammatory efficacy of a β2-adrenoceptor agonist in models of lung inflammation induced by cigarette smoke. The long-acting β2-adrenoceptor agonist olodaterol attenuated pulmonary inflammation through mechanisms that are separate from direct inhibition of bronchoconstriction. Furthermore, the in vivo data suggest that the anti-inflammatory properties of olodaterol are maintained after repeated dosing for 4 days.

Tiotropium/olodaterol versus tiotropium in Japanese patients with COPD: results from the DYNAGITO study

“…It is difficult to identify factors that might explain differences in rates of exacerbations requiring systemic corticosteroids or antibiotics. This may be related to the OLO-mediated anti-inflammatory effect, as previously described by Wex et al 19 It could also be because the decision to select between antibiotic and corticosteroid treatment, or a combination of the two, is made by the physician and is not based on formal standards set for the different types of exacerbation. However, systemic corticosteroid-treated events may represent more severe events than events treated with antibiotics alone, because systemic corticosteroid-treated events are associated with worse future outcomes.…”

CCR10+ILC2s with ILC1‐like properties exhibit a protective function in severe allergic asthma

“…Experiments with human tissues were approved by the regional independent ethics committee (Comité de Protection des Personnes Île de France VIII, Paris, France). Lung samples were obtained from 9 patients undergoing surgical resection at the Foch Hospital (Suresnes, France) for lung carcinoma who had not received preoperative anticancer chemotherapy . Lung lysates were obtained after digestion with collagenase D (Merck, Lyon, France) and filtration through a cell strainer prior to immediate flow cytometry analysis.…”

Evaluation of the anti-inflammatory effects of β-adrenoceptor agonists on human lung macrophages

“…In addition to bronchodilation, -agonists may also possess anti-inflammatory activity (Barnes, 2006;Theron et al, 2013). Both in vitro and in vivo studies suggest that -agonists may dampen inflammation although there are inconsistencies (Schild, 1937;O'Connor et al, 1994;Maris et al, 2004, Maris et al, 2005Bosmann et al, 2012;Wex et al, 2015). It is noteworthy that in many of these studies animal models or cell lines have been employed.…”