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.
| Publication Type | Academic Article |
| Authors | McElvaney N, Nakamura H, Birrer P, Hébert C, Wong W, Alphonso M, Baker J, Catalano M, Crystal R |
| Journal | J Clin Invest |
| Volume | 90 |
| Issue | 4 |
| Pagination | 1296-301 |
| Date Published | 10/01/1992 |
| ISSN | 0021-9738 |
| Keywords | Cystic Fibrosis, Inflammation, Interleukin-8, Proteins, Respiratory System, Serine Proteinase Inhibitors |
| Abstract | 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. |
| DOI | 10.1172/JCI115994 |
| PubMed ID | 1357002 |
| PubMed Central ID | PMC443173 |