Modulation of airway inflammation in cystic fibrosis. In vivo suppression of interleukin-8 levels on the respiratory epithelial surface by aerosolization of recombinant secretory leukoprotease inhibitor

J Clin Invest. 1992 Oct;90(4):1296-301. doi: 10.1172/JCI115994.


Based on the knowledge that neutrophil elastase (NE) in cystic fibrosis (CF) epithelial lining fluid (ELF) can induce human bronchial epithelial cells to express the gene for interleukin 8 (IL-8), an 8.5-kD neutrophil chemoattractant, we have evaluated CF ELF for the presence of IL-8, and investigated the ability of aerosolized recombinant secretory leukoprotease inhibitor (rSLPI) to suppress NE, and hence IL-8, levels on the respiratory epithelial surface in CF. Enzyme-linked immunoassay revealed 21.9 +/- 4.8 nM IL-8 in CF ELF compared with none in normals. Active NE was detectable in ELF of all individuals with CF and was significantly decreased (P < 0.03) after aerosolization of rSLPI. Human bronchial epithelial cells exposed to CF ELF recovered before rSLPI therapy expressed IL-8 mRNA transcripts, but ELF recovered after rSLPI therapy induced far less bronchial epithelial cell IL-8 gene expression. Consistent with this, rSLPI aerosol therapy caused a marked reduction in CF ELF IL-8 levels (P < 0.05) and neutrophil number (P < 0.02). There was also a clear association between CF ELF active NE and IL-8 levels (r = 0.94). These data suggest that rSLPI therapy not only suppresses respiratory epithelial NE levels, but also breaks a cycle of inflammation on the CF epithelial surface.

MeSH terms

  • Adult
  • Aerosols
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / drug therapy*
  • Dimercaprol / chemistry
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Female
  • Humans
  • Inflammation / prevention & control*
  • Interleukin-8 / analysis*
  • Interleukin-8 / genetics
  • Leukocyte Elastase
  • Male
  • Pancreatic Elastase / analysis
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Respiratory System / drug effects*
  • Respiratory System / metabolism
  • Serine Proteinase Inhibitors / administration & dosage
  • Serine Proteinase Inhibitors / therapeutic use*


  • Aerosols
  • Interleukin-8
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins
  • Recombinant Proteins
  • Serine Proteinase Inhibitors
  • Dimercaprol
  • Pancreatic Elastase
  • Leukocyte Elastase