Tyloxapol inhibits NF-kappa B and cytokine release, scavenges HOCI, and reduces viscosity of cystic fibrosis sputum.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ghio, AJ; Marshall, BC; Diaz, JL; Hasegawa, T; Samuelson, W; Povia, D; Kennedy, TP; Piantodosi, CA

Published Date

  • September 1996

Published In

Volume / Issue

  • 154 / 3 Pt 1

Start / End Page

  • 783 - 788

PubMed ID

  • 8810619

Pubmed Central ID

  • 8810619

International Standard Serial Number (ISSN)

  • 1073-449X

Digital Object Identifier (DOI)

  • 10.1164/ajrccm.154.3.8810619

Language

  • eng

Conference Location

  • United States