Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future)
British Journal of Pharmacology
Abstract
Background and purpose
Background and purpose
β2-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-agonist olodaterol to inhibit pulmonary inflammation and to shed light on its anti-inflammatory mechanism of action.
Experimental approach
Olodaterol was tested in murine and guinea pig models of cigarette smoke- and lipopolysaccharide-induced lung inflammation. Furthermore, effects of olodaterol on pro-inflammatory cytokine release from human parenchymal explants, on lipopolysaccharide-induced CD11b adhesion molecule expression on human granulocytes, on TNF-α release from human whole blood and on IL-8-induced migration of human peripheral blood neutrophils were investigated.
Key results
Olodaterol 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 relevant doses in terms of their bronchodilatory efficacy. Mechanistically, olodaterol attenuated pro-inflammatory mediator release from human parenchymal explants and whole blood and reduced the CD11b adhesion molecule expression on granulocytes, but had no direct effect on the IL-8-induced neutrophil transwell migration.
Conclusions and implication
We demonstrated for the first time the anti-inflammatory efficacy of a β2-adrenoceptor agonist in models of cigarette smoke-induced lung inflammation. Furthermore, we substantiated that the long-acting β2-agonist olodaterol attenuates pulmonary inflammation through additional mechanisms that are separate from direct inhibition of bronchoconstriction. Our in vivo data suggest that the anti-inflammatory properties of olodaterol are maintained after repeated dosing for four days.
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