Fluticasone and budesonide inhibit cytokine release in human lung epithelial cells and alveolar macrophages.
Glucocorticoids are potent anti-inflammatory agents capable of influencing cytokine release in a number of cell types. The aim of the present study was to investigate whether glucocorticoids, frequently used in the treatment of asthma, interfere with cytokine secretion by lung epithelial cells and alveolar macrophages in vitro. Inhalation of swine dust induces airway inflammation with influx of inflammatory cells and release of proinflammatory cytokines in the lungs. Therefore, human lung epithelial cells (A549) and human alveolar macrophages were stimulated with swine dust or lipopolysaccharide (LPS), and the inhibitory effect of budesonide and fluticasone propionate on cytokine release was studied in a dose-response (10(-13)-10(-8) M) manner. The time course for the steroid effect was also investigated. Both steroids caused a dose-dependent, almost total, inhibition of swine dust-induced IL-6 and IL-8 release from epithelial cells and LPS-induced IL-6 and TNF-alpha from alveolar macrophages. The steroids only partially inhibited IL-8 release from alveolar macrophages. Budesonide was approximately 10 times less potent than fluticasone propionate. Preincubation with the steroids did not inhibit cytokine release more than simultaneous incubation with stimulus and steroid. In conclusion, budesonide and fluticasone propionate, in concentrations that probably occur in the airway lining fluid during inhalational therapy, inhibited cytokine release from human lung epithelial cells (IL-6, IL-8) and alveolar macrophages (TNF-alpha, IL-6, IL-8). In vitro, the onset of this effect was rapid.
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Department of Occupational Medicine, National Institute for Working Life, Solna, Sweden.
Larsson
K
K
Siljerud
S
S
Palmberg
L
L
D000328:Adult; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D004391:Dust / Q000009:adverse effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology; D000068298:Fluticasone; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013552:Swine; D014407:Tumor Cells, Cultured
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004391:Dust; D008070:Lipopolysaccharides; D019819:Budesonide; D000068298:Fluticasone