Lipopolysaccharide exacerbates functional and inflammatory responses to ovalbumin and decreases sensitivity to inhaled fluticasone propionate in a guinea-pig model of asthma

Lowe, A. P. P., Thomas, R.S., Nials, A. T., Kidd, E.J. ORCID: https://orcid.org/0000-0001-5507-1170, Broadley, K.J. ORCID: https://orcid.org/0000-0002-3339-2050 and Ford, W.R. ORCID: https://orcid.org/0000-0002-8792-6169 2015. Lipopolysaccharide exacerbates functional and inflammatory responses to ovalbumin and decreases sensitivity to inhaled fluticasone propionate in a guinea-pig model of asthma. British Journal of Pharmacology 172 (10) , pp. 2588-2603. 10.1111/bph.13080

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Abstract

Background and Purpose Asthma exacerbations contribute to corticosteroid insensitivity. Lipopolysaccharide (LPS) is ubiquitous in the environment. It causes bronchoconstriction and airways inflammation and may therefore exacerbate allergen responses. This study examined whether LPS and ovalbumin co-administration could exacerbate the airways inflammatory and functional responses to ovalbumin in conscious guinea-pigs and whether these exacerbated responses were insensitive to inhaled corticosteroid treatment with fluticasone propionate. Experimental Approach Guinea-pigs were sensitized and challenged with ovalbumin and airways function recorded as specific airways conductance (sGaw) by whole body plethysmography. Airways inflammation was measured from lung histology and bronchoalveolar lavage. Airways hyperreactivity (AHR) to inhaled histamine was examined 24h after ovalbumin. LPS was inhaled alone or 24 or 48 hours before ovalbumin and combined with ovalbumin. Fluticasone propionate (0.05, 0.1, 0.5 or 1mg/ml) or vehicle (ethanol:DMSO:saline 30:30:40) was nebulised for 15 minutes twice daily for 6 days before ovalbumin or LPS exposure. Key Results Ovalbumin inhalation caused early (EAR) and late asthmatic responses (LAR), airways hypereactivity to histamine and influx of inflammatory cells into the lungs. LPS 48 hours before and co-administered with ovalbumin exacerbated the response with increased length of the EAR, prolonged response to histamine and elevated inflammatory cells. FP 0.5 and 1mg/ml reduced the LAR, AHR and cell influx with ovalbumin alone, but was ineffective when guinea-pigs were exposed to LPS before and with ovalbumin. Conclusions and Implications LPS exposure exacerbates airways inflammatory and functional responses to allergen inhalation and decreases corticosteroid sensitivity. Its widespread presence in the environment could contribute to asthma exacerbations and corticosteroid insensitivity in humans.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Additional Information:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license
Publisher:	Wiley
ISSN:	0007-1188
Funders:	MRC
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	6 January 2015
Last Modified:	23 May 2023 17:54
URI:	https://orca.cardiff.ac.uk/id/eprint/70226

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