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Tyloxapol inhibits NF-kappa B and cytokine release, scavenges HOCI, and reduces viscosity of cystic fibrosis sputum.
- Source :
-
American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 1996 Sep; Vol. 154 (3 Pt 1), pp. 783-8. - Publication Year :
- 1996
-
Abstract
- Cystic fibrosis (CF) patients develop progressive cytokine-mediated inflammatory lung disease, with abundant production of thick, tenacious, protease- and oxidant-rich purulent airway secretions that are difficult to clear even with physiotherapy. In the search for a potential treatment, we have tested tyloxapol, an alkylaryl polyether alcohol polymer detergent previously used as a mucolytic agent in adult chronic bronchitis. Tyloxapol inhibits activation of the transcription factor nuclear factor-kappa B (NK-kappa B), reduces resting secretion of the cytokine interleukin-8 (IL-8) in cultured human monocytes, and inhibits lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and the eiconsanoids thromboxane A2 and leukotriene B4 (LTB4). We have previously shown that tyloxapol is a potent antioxidant for hydroxyl radicals ( OH). Tyloxapol (0.05 to 0.1% wt/vol) effectively scavenges the oxidant hypochlorous acid (HOCl; 1 to 7.5 mM) in vitro, and protects from HOCl-mediated lung injury in rats. Tyloxapol also reduces the viscosity of CF sputum (from 463 +/- 133 to 128 +/- 52 centipoise). We conclude that tyloxapol is potentially useful as a new antiinflammatory therapy for CF lung disease, and could possibly promote clearance of secretions in the CF airway.
- Subjects :
- Adult
Animals
Base Sequence
Cells, Cultured
Cystic Fibrosis immunology
Cystic Fibrosis physiopathology
DNA metabolism
Free Radical Scavengers pharmacology
Humans
Hypochlorous Acid metabolism
Male
Molecular Sequence Data
Monocytes drug effects
Monocytes metabolism
Polyethylene Glycols therapeutic use
Rats
Rats, Sprague-Dawley
Sputum metabolism
Surface-Active Agents therapeutic use
Transcription Factors
Viscosity drug effects
Cystic Fibrosis drug therapy
Cytokines metabolism
NF-kappa B metabolism
Polyethylene Glycols pharmacology
Sputum drug effects
Surface-Active Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1073-449X
- Volume :
- 154
- Issue :
- 3 Pt 1
- Database :
- MEDLINE
- Journal :
- American journal of respiratory and critical care medicine
- Publication Type :
- Academic Journal
- Accession number :
- 8810619
- Full Text :
- https://doi.org/10.1164/ajrccm.154.3.8810619