Evaluation of the anti-inflammatory effects of β-adrenoceptor agonists on human lung macrophages

• Published in: European journal of pharmacology 2016-12, Vol.793, p.49-55
• Main Authors: Gill, Sharonjit K, Marriott, Helen M, Suvarna, S Kim, Peachell, Peter T
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Agonists - pharmacology; Adult; Aged; Aged, 80 and over; Alveolar macrophages; Anti-Inflammatory Agents - pharmacology; Cytokines - biosynthesis; Cytokines - secretion; Female; Humans; Indacaterol; Indans - pharmacology; Lung - cytology; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Macrophages - secretion; Male; Middle Aged; Monocytes - cytology; Quinolones - pharmacology; Salmeterol; Time Factors; TNFα; β-agonists
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2016.11.005

The principal mechanism by which bronchodilator β-adrenoceptor agonists act is to relax airways smooth muscle although they may also be anti-inflammatory. However, the extent of anti-inflammatory activity and the cell types affected by these agonists are uncertain. The purpose of this study was to evaluate whether β-adrenoceptor agonists prevent pro-inflammatory cytokine generation from activated human lung macrophages. Macrophages were isolated and purified from human lung. The cells were pre-treated with both short-acting (isoprenaline, salbutamol, terbutaline) and long-acting (formoterol, salmeterol, indacaterol) β-agonists before activation with lipopolysaccharide (LPS) to induce cytokine (TNFα, IL-6, IL-8 and IL-10) generation. The experiments showed that short-acting β-agonists were poor inhibitors of cytokine generation. Of the long-acting β-agonists studied, formoterol was also a weak inhibitor of cytokine generation whereas only indacaterol and salmeterol showed moderate inhibitory activity. Further experiments using the β2-adrenoceptor antagonist ICI-118,551 suggested that the effects of indacaterol were likely to be mediated by β2-adrenoceptors whereas those of salmeterol were not. These findings were corroborated by functional desensitization studies in which the inhibitory effects of indacaterol appeared to be receptor-mediated whereas those of salmeterol were not. Taken together, the data indicate that the anti-inflammatory effects of β-adrenoceptor agonists on human lung macrophages are modest.