Inhaled corticosteroids and beta-agonists inhibit oxidant production by bronchoalveolar lavage cells from normal volunteers in vivo.
To study the anti-inflammatory mechanisms of inhaled corticosteroids and beta-agonist therapies, we evaluated basal and stimulus-induced superoxide production by human airway inflammatory cells obtained by bronchoalveolar lavage from normal volunteers before and after 3 weeks of an inhaled corticosteroid (flunisolide) and beta-agonist (metaproterenol). Assay of superoxide production by the bronchoalveolar lavage cells was performed in the presence of media alone or media containing phorbol ester by optical density determination of reduced ferricytochrome c at 550 nm. Interleukin-1 beta released from unstimulated cells and cells stimulated with lipopolysaccharide was quantitated by enzyme immunoassay. Interestingly, phorbol ester-stimulated superoxide production was strikingly inhibited (P < 0.05) by inhaled therapies, while stimulus induced Interleukin-1 beta production was not significantly affected (P = 0.12). Suppression of oxidant production by airway inflammatory cells may be a major mechanism for the beneficial anti-inflammatory effects of inhaled corticosteroids and beta-agonists.
Dweik
R A
RA
Department of Pulmonary Medicine, Cleveland Clinic Foundation, OH 44195, USA. dweikr@cesmtp.ccf.org
Lewis
M
M
Kavuru
M
M
Buhrow
L
L
Erzurum
S C
SC
Thomassen
M J
MJ
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D005446:Fluocinolone Acetonide / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009921:Metaproterenol / Q000494:pharmacology*; D016877:Oxidants / Q000096:biosynthesis*; D013268:Stimulation, Chemical; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016877:Oxidants; D005446:Fluocinolone Acetonide; D013481:Superoxides; D009921:Metaproterenol; C007734:flunisolide; D013755:Tetradecanoylphorbol Acetate