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POSTER PRESENTATION Open Access Assessment of the time course of chronic inflammation in the murine house dust mite model Stephen M Jordan 1* , Robert Carrington 1 , David Lanham 2 , James Cartwright 3 , Rachel A Armstrong 1 , Kenneth G Meecham 1 From 2nd Cross Company Respiratory Symposium Horsham, UK. 6-7 September 2012 House dust mite (HDM) allergens are associated with allergic disorders and the use of this clinically relevant allergen is increasing in animal models. We assessed the chronic inflammatory time course and the anti-inflamma- tory efficacy of a phosphodiesterase 4 inhibitor and a corti- costeroid. BALB/c mice were challenged intranasally with HDM for 5 days/week for 5 weeks. Animals were sacri- ficed weekly 24 hours after final challenge and recruitment of inflammatory cells assessed in bronchoalveolar lavage fluid (BALF). Lung tissue was stained for the evaluation of a histopathological response. Roflumilast (10 mg/kg) and prednisolone (10 mg/kg) were administered orally twice daily from Week 3. Chronic HDM extract exposure resulted in significant recruitment of eosinophils, neutro- phils, lymphocytes and macrophages as early as Week 1, peaking (1.13±032, 0.31±0.05, 0.66±0.10 and 0.33±0.04 x10 6 cells/animal respectively) between Weeks 3 and 5. Within the lymphocyte population the proportion of B cells increased from 4 to 46% over the 5 week exposure period. Mice developed perivascular, peribronchiolar and alveolar inflammation which increased in severity during the five week exposure period. The inflammation was accompanied by epithelial and mucus cell hypertrophy/ hyperplasia in the bronchi and bronchioles which reached maximum severity during Weeks 3 to 5. Perivascular/peri- bronchiolar fibrosis peaked in Week 5. Therapeutic treat- ment with prednisolone and roflumilast significantly (P<0.001) inhibited BALF cell recruitment and reduced the severity of the airway remodelling suggesting this model, in our laboratory, has the potential to test novel compounds for the treatment of allergic disorders. Authorsdetails 1 Department of Pharmacology, Huntingdon Life Sciences, Cambridgeshire, UK. 2 Department of Biomarkers, Bioanalysis and Clinical Sciences, Huntingdon Life Sciences, Cambridgeshire, UK. 3 Department of Pathology, Huntingdon Life Sciences, Cambridgeshire, UK. Published: 14 August 2013 doi:10.1186/1476-9255-10-S1-P1 Cite this article as: Jordan et al.: Assessment of the time course of chronic inflammation in the murine house dust mite model. Journal of Inflammation 2013 10(Suppl 1):P1. Submit your next manuscript to BioMed Central and take full advantage of: Convenient online submission Thorough peer review No space constraints or color figure charges Immediate publication on acceptance Inclusion in PubMed, CAS, Scopus and Google Scholar Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit 1 Department of Pharmacology, Huntingdon Life Sciences, Cambridgeshire, UK Full list of author information is available at the end of the article Jordan et al. Journal of Inflammation 2013, 10(Suppl 1):P1 http://www.journal-inflammation.com/content/10/S1/P1 © 2013 Jordan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Assessment of the time course of chronic inflammation in the murine house dust mite model

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POSTER PRESENTATION Open Access

Assessment of the time course of chronicinflammation in the murine house dust mite modelStephen M Jordan1*, Robert Carrington1, David Lanham2, James Cartwright3, Rachel A Armstrong1,Kenneth G Meecham1

From 2nd Cross Company Respiratory SymposiumHorsham, UK. 6-7 September 2012

House dust mite (HDM) allergens are associated withallergic disorders and the use of this clinically relevantallergen is increasing in animal models. We assessed thechronic inflammatory time course and the anti-inflamma-tory efficacy of a phosphodiesterase 4 inhibitor and a corti-costeroid. BALB/c mice were challenged intranasally withHDM for 5 days/week for 5 weeks. Animals were sacri-ficed weekly 24 hours after final challenge and recruitmentof inflammatory cells assessed in bronchoalveolar lavagefluid (BALF). Lung tissue was stained for the evaluation ofa histopathological response. Roflumilast (10 mg/kg) andprednisolone (10 mg/kg) were administered orally twicedaily from Week 3. Chronic HDM extract exposureresulted in significant recruitment of eosinophils, neutro-phils, lymphocytes and macrophages as early as Week 1,peaking (1.13±032, 0.31±0.05, 0.66±0.10 and 0.33±0.04x106cells/animal respectively) between Weeks 3 and 5.Within the lymphocyte population the proportion of Bcells increased from 4 to 46% over the 5 week exposureperiod. Mice developed perivascular, peribronchiolar andalveolar inflammation which increased in severity duringthe five week exposure period. The inflammation wasaccompanied by epithelial and mucus cell hypertrophy/hyperplasia in the bronchi and bronchioles which reachedmaximum severity during Weeks 3 to 5. Perivascular/peri-bronchiolar fibrosis peaked in Week 5. Therapeutic treat-ment with prednisolone and roflumilast significantly(P<0.001) inhibited BALF cell recruitment and reducedthe severity of the airway remodelling suggesting thismodel, in our laboratory, has the potential to test novelcompounds for the treatment of allergic disorders.

Authors’ details1Department of Pharmacology, Huntingdon Life Sciences, Cambridgeshire,UK. 2Department of Biomarkers, Bioanalysis and Clinical Sciences,Huntingdon Life Sciences, Cambridgeshire, UK. 3Department of Pathology,Huntingdon Life Sciences, Cambridgeshire, UK.

Published: 14 August 2013

doi:10.1186/1476-9255-10-S1-P1Cite this article as: Jordan et al.: Assessment of the time course ofchronic inflammation in the murine house dust mite model. Journal ofInflammation 2013 10(Suppl 1):P1.

Submit your next manuscript to BioMed Centraland take full advantage of:

• Convenient online submission

• Thorough peer review

• No space constraints or color figure charges

• Immediate publication on acceptance

• Inclusion in PubMed, CAS, Scopus and Google Scholar

• Research which is freely available for redistribution

Submit your manuscript at www.biomedcentral.com/submit

1Department of Pharmacology, Huntingdon Life Sciences, Cambridgeshire,UKFull list of author information is available at the end of the article

Jordan et al. Journal of Inflammation 2013, 10(Suppl 1):P1http://www.journal-inflammation.com/content/10/S1/P1

© 2013 Jordan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.