Evaluation of the anti-inflammatory effects of β-adrenoceptor agonists on human lung macrophages.
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.
Academic Unit of Respiratory Medicine, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, The Medical School (Floor L), Beech Hill Road, Sheffield S10 2RX, UK.
Sharonjit K
SK
Gill
Academic Unit of Respiratory Medicine, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, The Medical School (Floor L), Beech Hill Road, Sheffield S10 2RX, UK.
Helen M
HM
Marriott
Histopathology Department, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK.
S Kim
SK
Suvarna
Academic Unit of Respiratory Medicine, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, The Medical School (Floor L), Beech Hill Road, Sheffield S10 2RX, UK. Electronic address: p.t.peachell@shef.ac.uk.
Peter T
PT
Peachell
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D006801:Humans; D007189:Indans / Q000494:pharmacology; D008168:Lung / Q000166:cytology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D015363:Quinolones / Q000494:pharmacology; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007189:Indans; D015363:Quinolones; C510790:indacaterol
Alveolar macrophages; Indacaterol; Salmeterol; TNFα; β-agonists