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 - 04/09/11
Corresponding author. Tel.: +49 4102 8881 122; fax: +49 4102 8881 113.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).
Le texte complet de cet article est disponible en PDF.Keywords : Pan-selectin antagonist, Human ozone challenge model, Pulmonary inflammation
Plan
Vol 24 - N° 5
P. 555-558 - octobre 2011 Retour au numéro
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