Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?
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.
['Theron|Annette J|AJ|', 'Steel|Helen C|HC|', 'Tintinger|Gregory R|GR|', 'Feldman|Charles|C|', 'Anderson|Ronald|R|']
D058666:Adrenergic beta-2 Receptor Agonists D000818:Animals D000893:Anti-Inflammatory Agents D005786:Gene Expression Regulation D006801:Humans D007249:Inflammation D018836:Inflammation Mediators D018343:Receptors, Adrenergic, beta-2 D015398:Signal Transduction D016896:Treatment Outcome
adenylyl cyclase corticosteroids cyclic AMP muscarinic receptor antagonists neutrophils phosphodiesterase inhibitors