Efficacy of the pan-selectin antagonist Bimosiamose on ozone-induced airway inflammation in healthy subjects--a double blind, randomized, placebo-controlled, cross-over clinical trial.

Abstract

Selectins, a family of cell adhesion molecules, are involved in the activation and extravasation of leukocytes in inflammatory diseases. Inhalation of ozone induces an inflammation of the airways, which is dominated by neutrophils. We investigated the effect of repeated inhalations of the pan-selectin antagonist Bimosiamose on ozone-induced airway inflammation in healthy volunteers. In a double-blind, placebo-controlled, randomized, cross-over study Bimosiamose (10 mg bid) was inhaled via a breath actuated nebulizer (AKITA2 APIXNEB(®)) for 4 days. Treatment was followed by inhalation of ozone (250 ppb) for 3 h with intermittent exercise. Induced sputum was collected 3 h post ozone challenge for analysis of cellular and non-cellular composition. 18 subjects were randomized and completed the study. All treatments were safe and well tolerated. Compared to placebo Bimosiamose reduced the numbers of sputum neutrophils by 40% (p = 0.068) and concentrations of interleukin-8 and matrix-metalloproteinase-9 in sputum supernatant by 35% (p = 0.004) and 46% (p = 0.022), respectively. Inhalation of Bimosiamose showed favourable anti-inflammatory effects on ozone-induced airway inflammation in healthy volunteers. Further studies have to proof and translate this anti-inflammatory effect of Bimosiamose into a clinical benefit in patients with chronic obstructive pulmonary disease. (ClinTrialgov Ident: NCT01108913).

• Authors: Anne Kirsten, Henrik Watz, Gunther Kretschmar, Frauke Pedersen, Daniel Bock, Wolfgang Meyer-Sabellek, Helgo Magnussen
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 24 Issue 5 Pg. 555-8 (Oct 2011) ISSN: 1522-9629 [Electronic] England
• PMID: 21514398 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Hexanes
• Interleukin-8
• Ozone
• bimosiamose
• Matrix Metalloproteinase 9
• Mannose

Topics

• Adult
• Cross-Over Studies
• Double-Blind Method
• Exercise Test
• Female
• Hexanes (adverse effects, pharmacology)
• Humans
• Inflammation (drug therapy, etiology)
• Inhalation Exposure
• Interleukin-8 (drug effects, metabolism)
• Male
• Mannose (adverse effects, analogs & derivatives, pharmacology)
• Matrix Metalloproteinase 9 (drug effects, metabolism)
• Middle Aged
• Nebulizers and Vaporizers
• Neutrophils (immunology)
• Ozone (adverse effects)
• Respiratory System (drug effects, pathology)
• Sputum (immunology)