Tyloxapol inhibits NF-κB and cytokine release, scavenges HOCl, and reduces viscosity of cystic fibrosis sputum

Andrew J. Ghio, Bruce C. Marshall, Jose L. Diaz, Takashi Hasegawa, Wayne Samuelson, Daniel Povia, Thomas P. Kennedy, Claude A. Piantadosi

Research output: Contribution to journalArticle

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 (N K- κB), reduces resting secretion of the cytokine interleukin-8 (IL-8) in cultured human monocytes, and inhibits lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor-α (TNF-α), IL-1β, 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.

Original languageEnglish (US)
Pages (from-to)783-788
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume154
Issue number3 I
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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