title: The long-acting β2 -adrenoceptor agonist olodaterol attenuates pulmonary inflammation.
abstract: OBJECTIVE
  β2 -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.
  
  
  METHODS
  Olodaterol 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.
  
  
  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 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
  This 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.
authors.affiliation: Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Wex
authors.affiliation: Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Kollak
authors.affiliation: Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Duechs
authors.affiliation: UPRES EA 220 and Clinical Research Department, Foch Hospital, University of Versailles Saint-Quentin, Suresnes, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Naline
authors.affiliation: Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Wollin
authors.affiliation: UPRES EA 220 and Clinical Research Department, Foch Hospital, University of Versailles Saint-Quentin, Suresnes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Devillier
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008171:Lung Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D012907:Smoking; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D048588:Benzoxazines; D008070:Lipopolysaccharides; D018343:Receptors, Adrenergic, beta-2; D014409:Tumor Necrosis Factor-alpha; C549647:olodaterol
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