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Review
. 2013 Nov 22:7:1387-98.
doi: 10.2147/DDDT.S50995. eCollection 2013.

Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?

Annette J Theron  1 , Helen C Steel, Gregory R Tintinger, Charles Feldman, Ronald Anderson
Affiliations
Review

Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?

Annette J Theron et al. Drug Des Devel Ther. .

Abstract

Beta2-adrenoreceptor agonists (β2-agonists) are primarily bronchodilators, targeting airway smooth muscle and providing critical symptomatic relief in conditions such as bronchial asthma and chronic obstructive pulmonary disease. These agents also possess broad-spectrum, secondary, anti-inflammatory properties. These are mediated largely, though not exclusively, via interactions with adenylyl cyclase-coupled β2-adrenoreceptors on a range of immune and inflammatory cells involved in the immunopathogenesis of acute and chronic inflammatory disorders of the airways. The clinical relevance of the anti-inflammatory actions of β2-agonists, although often effective in the experimental setting, remains contentious. The primary objectives of the current review are: firstly, to assess the mechanisms, both molecular and cell-associated, that may limit the anti-inflammatory efficacy of β2-agonists; secondly, to evaluate pharmacological strategies, several of which are recent and innovative, that may overcome these limitations. These are preceded by a consideration of the various types of β2-agonists, their clinical applications, and spectrum of anti-inflammatory activities, particularly those involving adenosine 3',5'-cyclic adenosine monophosphate-activated protein kinase-mediated clearance of cytosolic calcium, and altered gene expression in immune and inflammatory cells.

Keywords: adenylyl cyclase; corticosteroids; cyclic AMP; muscarinic receptor antagonists; neutrophils; phosphodiesterase inhibitors.

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