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‐α) 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‐α 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.

[1]  L. Palmberg,et al.  Fluticasone and budesonide inhibit cytokine release in human lung epithelial cells and alveolar macrophages , 1999, Allergy.

[2]  Ek,et al.  Swine dust induces cytokine secretion from human epithelial cells and alveolar macrophages , 1999, Clinical and experimental immunology.

[3]  D. Gavhed,et al.  Inhalation of cold air increases the number of inflammatory cells in the lungs in healthy subjects. , 1998, The European respiratory journal.

[4]  L. Palmberg,et al.  Induction of IL-8 production in human alveolar macrophages and human bronchial epithelial cells in vitro by swine dust , 1998, Thorax.

[5]  W. Seeger,et al.  Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia. , 1998, The European respiratory journal.

[6]  D. Schwartz,et al.  The effect of of glucocorticoids on grain dust-induced airway disease. , 1998, Chest.

[7]  A. Kavelaars,et al.  β 2-Adrenergic activation enhances interleukin-8 production by human monocytes , 1997, Journal of Neuroimmunology.

[8]  L. Palmberg,et al.  Effect of exposure to swine dust on levels of IL-8 in airway lavage fluid. , 1997, Thorax.

[9]  L. Palmberg,et al.  Inhalation of swine dust induces cytokine release in the upper and lower airways. , 1997, The European respiratory journal.

[10]  J. Ancochea,et al.  [Bronchoalveolar lavage]. , 1997, Archivos de bronconeumologia.

[11]  A. Kavelaars,et al.  Beta 2-adrenergic activation enhances interleukin-8 production by human monocytes. , 1997, Journal of neuroimmunology.

[12]  Anders Lindén.  Increased interleukin‐8 release by β‐adrenoceptor activation in human transformed bronchial epithelial cells , 1996, British journal of pharmacology.

[13]  J. Cavaillon.  The nonspecific nature of endotoxin tolerance. , 1995, Trends in microbiology.

[14]  H. Ziegler-Heitbrock.  Molecular mechanism in tolerance to lipopolysaccharide. , 1995, Journal of inflammation.

[15]  L. Hansson,et al.  Swine dust causes intense airways inflammation in healthy subjects. , 1994, American journal of respiratory and critical care medicine.

[16]  T. Sandström,et al.  Differences in bronchoalveolar cell response to nitrogen dioxide exposure between smokers and nonsmokers. , 1994, The European respiratory journal.

[17]  T. Lee,et al.  Selective enhancement of GM-CSF, TNF-alpha, IL-1 beta and IL-8 production by monocytes and macrophages of asthmatic subjects. , 1994, The European respiratory journal.

[18]  M. Lohmann‐Matthes,et al.  Pulmonary macrophages. , 1994, The European respiratory journal.

[19]  G. Fantuzzi,et al.  Early down-regulation of TNF production by LPS tolerance in human monocytes: comparison with IL-1 beta, IL-6, and IL-8. , 1993, Lymphokine and cytokine research.

[20]  R. Dahl,et al.  Respiratory symptoms in Danish farmers: an epidemiological study of risk factors. , 1988, Thorax.

[21]  L. Perloff,et al.  The role of neutrophils in inflammation. , 1971, Pennsylvania medicine.