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

N. G. McElvaney, H. Nakamura, P. Birrer, C. A. Hébert, W. L. Wong, M. Alphonso, J. B. Baker, M. A. Catalano, Ronald Crystal

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1296-1301
Number of pages6
JournalJournal of Clinical Investigation
Volume90
Issue number4
DOIs
Publication statusPublished - 1 Jan 1992
Externally publishedYes

Fingerprint

Secretory Leukocyte Peptidase Inhibitor
Interleukin-8
Cystic Fibrosis
Leukocyte Elastase
Inflammation
Epithelial Cells
Neutrophils
Chemotactic Factors
Therapeutics
Aerosols
Immunoenzyme Techniques

Keywords

  • Aerosol therapy
  • Antiprotease
  • Cytokine
  • Neutrophil chemoattractant
  • Neutrophil elastase

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. / McElvaney, N. G.; Nakamura, H.; Birrer, P.; Hébert, C. A.; Wong, W. L.; Alphonso, M.; Baker, J. B.; Catalano, M. A.; Crystal, Ronald.

In: Journal of Clinical Investigation, Vol. 90, No. 4, 01.01.1992, p. 1296-1301.

Research output: Contribution to journalArticle

McElvaney, N. G. ; Nakamura, H. ; Birrer, P. ; Hébert, C. A. ; Wong, W. L. ; Alphonso, M. ; Baker, J. B. ; Catalano, M. A. ; Crystal, Ronald. / 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. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 4. pp. 1296-1301.
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