title: Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?
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.
authors.affiliation: Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, South Africa ; Tshwane Academic Division of the National Health Laboratory Service, Pretoria, South Africa.
authors.forename: Annette J
authors.initials: AJ
authors.lastname: Theron
authors.forename: Helen C
authors.initials: HC
authors.lastname: Steel
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Tintinger
authors.forename: Charles
authors.initials: C
authors.lastname: Feldman
authors.forename: Ronald
authors.initials: R
authors.lastname: Anderson
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D018343:Receptors, Adrenergic, beta-2
keywords: adenylyl cyclase; corticosteroids; cyclic AMP; muscarinic receptor antagonists; neutrophils; phosphodiesterase inhibitors