Use of secretory leukoprotease inhibitor to augment lung antineutrophil elastase activity.
Physiologically, secretory leukoprotease inhibitor (SLPI) is the major antiprotease of the epithelium of the upper respiratory tract providing protection against neutrophil elastase (NE). The recombinant form of SLPI (rSLPI) has several advantages compared with alpha 1-antitrypsin that make it interesting as potential therapy. In vitro, rSLPI proves to be an excellent inhibitor of NE. When administered as an aerosol in vitro and in vivo, the structure and function of rSLPI remain intact. Using the aerosol route, the half-life of rSLPI in respiratory epithelial lining fluid is 12 h; thus, giving it twice daily should guarantee satisfactory levels in the lung. Following inhalation, rSLPI moves from the epithelium in an intact form into the interstitium of the lung. Following on from these in vitro and in vivo experiments, a short-term study in patients with cystic fibrosis was performed with aerosolized rSLPI. Promising results relative to NE level reduction and the consequences for the inflammatory process in the bronchi were achieved. rSLPI not only induced an increase of the anti-NE protective screen, but also improved the antioxidant protection by raising glutathione levels in the lung in sheep. rSLPI may therefore provide a unique opportunity for protecting the lung from the damage caused by inflammatory processes by giving a single drug.
Vogelmeier
C
C
Pneumologische Abteilung, Medizinische Klinik I, Klinikum, Grosshadern, Ludwig-Maximilians-Universität München, Germany.
Gillissen
A
A
Buhl
R
R
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*
D000975:Antioxidants; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors; D019272:Leukocyte Elastase; D005978:Glutathione