Authors: Ravensberg, A. J.; Luijk, B.; Westers, P.¹; Hiemstra, P. S.²; Sterk, P. J.²; Lammers, J. W.³; Rabe, K. F.²

Source: Allergy, Volume 61, Number 9, September 2006 , pp. 1097-1103(7)

Publisher: Wiley-Blackwell

Abstract:

Adhesion molecule very late antigen-4 (VLA-4) is implicated in the recruitment and activation of inflammatory cells in asthma, including eosinophils, T cells and mast cells. VLA-4 antagonists have been proposed as a new anti-inflammatory treatment modality for asthma. Therefore, we investigated whether a single inhaled dose of VLA-4 antagonist GW559090X could protect against allergen-induced changes in airway responses and airway inflammation in patients with asthma. We performed a randomized, double-blind, three-way crossover study with single inhaled doses of 3 mg of GW559090X, 500 μg of fluticasone propionate (FP) or placebo in 15 patients with mild intermittent asthma, controlled with short-acting β₂-agonists only. All patients developed a late asthmatic response (LAR) after allergen inhalation during screening. Study medication was administered 30 min prior to allergen challenge. Pre-dose and 24 h post-dose PC₂₀ methacholine and levels of exhaled nitric oxide (eNO) were determined. At the given dose, VLA-4 antagonist GW559090X did not attenuate the early asthmatic response (EAR) when compared with placebo: mean AUC_0−2h(± SEM) (%fall h): 27.2 ± 3.7 and 21.9 ± 3.0 respectively (P = 0.33); nor the LAR: mean AUC_3−8h(± SEM) (%fall h): 98.8 ± 12.9 and 94.8 ± 6.8 respectively (P = 0.84). However, pretreatment with FP did attenuate both EAR and LAR when compared with placebo: mean AUC_0−2h11.6 ± 3.3 (P = 0.024) and mean AUC_3−8h 6.3 ± 7.6 (P < 0.001). None of these treatments had an effect on allergen-induced changes in airway hyper-responsiveness or eNO levels. These findings suggest that VLA-4 may not play a major role in allergen-induced airway responses and inflammation in asthma.

Keywords: airway inflammation; anti-inflammatory agent; asthma; bronchial allergen challenge; very late antigen 4

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1398-9995.2006.01146.x

Affiliations: 1: Centre for Biostatistics, Utrecht University, Utrecht, The Netherlands 2: Pulmonology, Leiden University Medical Center, Leiden 3: Pulmonology, University Medical Center Utrecht

Publication date: 2006-09-01

Related content

• In this: publication
• By this: publisher
• In this Subject: Allergy & Immunology
• By this author: Ravensberg, A. J. ;  Luijk, B. ;  Westers, P. ;  Hiemstra, P. S. ;  Sterk, P. J. ;  Lammers, J. W. ;  Rabe, K. F.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers