Influence of fluticasone and salmeterol on airway effects of inhaled organic dust;an in vivo and ex vivo study.
Inhalation of dust from swine confinement buildings induces airway inflammation with an increase in both inflammatory cell numbers and secretion of proinflammatory cytokines in the lungs. It is not known whether anti-asthma drugs, which influence airway inflammation in asthma, also influence the airway reaction to inhaled organic dust. In the present study we examined the effects of a ss2-agonist (salmeterol) and an inhaled steroid (fluticasone) on the swine dust-induced cell and cytokine content of the lower airways, and cytokine release in cultured alveolar macrophages. Healthy volunteers were pretreated with inhaled salmeterol (n = 8), fluticasone propionate (n = 8) or placebo (n = 8) for about 2 weeks and exposed to dust in a pig house. Bronchoalveolar lavage was performed both before medication and after dust exposure. Cell differential counts and cytokine analyses in bronchoalveolar lavage fluid (BALF) were examined. Alveolar macrophages were cultured and cytokine release was studied, both in unstimulated cells and after lipopolysaccharide (LPS) stimulation. Unstimulated alveolar macrophages from swine dust-exposed individuals released less IL-6, IL-8 and tumour necrosis factor-alpha (TNF-alpha) after, than before, exposure (P < 0.01). Medication did not influence basal cytokine production. Fluticasone inhibited LPS-induced IL-6 and IL-8 release (P < 0.05). There was no significant difference between the groups. There was a large and significant increase (P < 0.05) in alveolar macrophage, granulocyte, lymphocyte numbers, and IL-6 and TNF-alpha content in BALF in all three groups following dust exposure, with no significant difference between the groups. These findings suggest that drugs which are known to influence and control airway inflammation in asthma do not have major effects on airway inflammation induced by the inhalation of organic dust.
Ek
A
A
Program for Respiratory Health and Climate, National Institute for Working Life, Stockholm, Sweden. aek@niwl.se
Palmberg
L
L
Larsson
K
K
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000485:Allergens / Q000276:immunology; D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D004391:Dust; D000068298:Fluticasone; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000068299:Salmeterol Xinafoate; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000485:Allergens; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D004391:Dust; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol