The long-acting β2 -adrenoceptor agonist olodaterol attenuates pulmonary inflammation.

Abstract

BACKGROUND AND PURPOSE:

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.

EXPERIMENTAL APPROACH:

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.

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 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 IMPLICATIONS:

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: Eva Wex, Ines Kollak, Matthias J Duechs, Emmanuel Naline, Lutz Wollin, Philippe Devillier
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 172 Issue 14 Pg. 3537-47 (Jul 2015) ISSN: 1476-5381 [Electronic] England
• PMID: 25824824 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

Chemical References

• Adrenergic beta-2 Receptor Agonists
• Benzoxazines
• Lipopolysaccharides
• Receptors, Adrenergic, beta-2
• Tumor Necrosis Factor-alpha
• olodaterol

Topics

• Adrenergic beta-2 Receptor Agonists (administration & dosage, pharmacology)
• Animals
• Benzoxazines (administration & dosage, pharmacology)
• Cell Movement (drug effects)
• Dose-Response Relationship, Drug
• Granulocytes (drug effects, metabolism)
• Guinea Pigs
• Humans
• Inflammation (drug therapy, metabolism)
• Lipopolysaccharides (antagonists & inhibitors, pharmacology)
• Lung Diseases (drug therapy, metabolism, pathology)
• Mice
• Neutrophils (drug effects, metabolism)
• Receptors, Adrenergic, beta-2 (metabolism)
• Smoking
• Structure-Activity Relationship
• Tumor Necrosis Factor-alpha (metabolism)