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O04 - Effects of 5-lipoxygenase pathway inhibition on rhinovirus-associated bronchial epithelial inflammation


Human bronchial epithelial cells produce a variety of inflammatory mediators upon exposure to rhinovirus (RV), a major precipitant of asthma exacerbations. We hypothesized that anti-leukotriene (LT) treatment of epithelial cells with or without exposure to supernatants of RV-infected peripheral blood mononuclear cells (PBMCs) may inhibit RV-induced up-regulation of inflammatory cytokines.


PBMCs were isolated from a non-atopic, non-asthmatic donor and exposed to 1MOI of RV-1B, and supernatants were harvested at 48h post-infection. Subsequently, BEAS-2B, a bronchial epithelial cell line, was infected with RV, with or without conditioning with PBMC supernatants. Treatment with anti-LT agents was performed either on both PBMCs and BEAS-2B or at the bronchial epithelial level only, with varying concentrations of montelukast or MK-886. We evaluated the concentration of inflammatory cytokines (IL-8, RANTES, IL-11, IL-6 and IP-10) in culture supernatants at 48 hours after infection of BEAS-2B cells with the use of commercially available immunoassays.


Treatment of PBMCs and BEAS-2B with montelukast at concentrations of 10-4M to 10-6M, and with MK-886 at a concentration of 10-4M significantly inhibited release of IL-8 by RV-infected BEAS-2B. RANTES, IL-6 and IP-10 release was inhibited at all concentrations tested by both drugs, while IL-11 release was inhibited only after treatment with montelukast. Treatment of BEAS-2B cells with montelukast or with MK-886 at a concentration of 10-6M inhibited release of all cytokines measured, irrespective of exposure to conditioned media of RV-infected PBMCs, while 10-9M montelukast inhibited the release of IL-8, IL-11 and IL-6, and 10-9M MK-886 suppressed the release of IL-8 and RANTES.


Our results show that anti-LT treatment of RV-infected bronchial epithelial cells, with or without exposure to conditioned media of RV-infected PBMCs suppresses epithelial RV-mediated inflammatory cytokine production. Our observations may represent an indirect mode of action of anti-leukotriene medication in virus-induced asthma.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Spyridaki, I., Skevaki, C., Trochoutsou, A. et al. O04 - Effects of 5-lipoxygenase pathway inhibition on rhinovirus-associated bronchial epithelial inflammation. Clin Transl Allergy 4 (Suppl 1), O4 (2014).

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