- Title
- Dynamics of IL-4 and IL-13 expression in the airways of sheep following allergen challenge
- Creator
- Liravi, Bahar; Piedrafita, David; Nguyen, Gary; Bischof, Robert
- Date
- 2015
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/155122
- Identifier
- vital:11270
- Identifier
-
https://doi.org/10.1186/s12890-015-0097-9
- Identifier
- ISSN:1471-2466
- Abstract
- Background: IL-4 and IL-13 play a critical yet poorly understood role in orchestrating the recruitment and activation of effector cells of the asthmatic response and driving the pathophysiology of allergic asthma. The house dust mite (HDM) sheep asthma model displays many features of the human condition and is an ideal model to further elucidate the involvement of these critical Th
2 cytokines. We hypothesized that airway exposure to HDM allergen would induce or elevate the expression profile of IL-4 and IL-13 during the allergic airway response in this large animal model of asthma. Methods: Bronchoalveolar lavage (BAL) samples were collected from saline-and house dust mite (HDM)-challenged lung lobes of sensitized sheep from 0 to 48h post-challenge. BAL cytokines (IL-4, IL-13, IL-6, IL-10, TNF-aα) were each measured by ELISA. IL-4 and IL-13 expression was assessed in BAL leukocytes by flow cytometry and in airway tissue sections by immunohistology. Results: IL-4 and IL-13 were increased in BAL samples following airway allergen challenge. HDM challenge resulted in a significant increase in BAL IL-4 levels at 4h compared to saline-challenged airways, while BAL IL-13 levels were elevated at all time-points after allergen challenge. IL-6 levels were maintained following HDM challenge but declined after saline challenge, while HDM administration resulted in an acute elevation in IL-10 at 4h but no change in TNF-aα levels over time. Lymphocytes were the main early source of IL-4, with IL-4 release by alveolar macrophages (AMs) prominent from 24h post-allergen challenge. IL-13 producing AMs were increased at 4 and 24h following HDM compared to saline challenge, and tissue staining provided evidence of IL-13 expression in airway epithelium as well as immune cells in airway tissue. Conclusion: In a sheep model of allergic asthma, airway inflammation is accompanied by the temporal release of key cytokines following allergen exposure that primarily reflects the Th2 -driven nature of the immune response in asthma. The present study demonstrates for the first time the involvement of IL-4 and IL-13 in a relevant large animal model of allergic airways disease. © 2015 Liravi et al. - Publisher
- BioMed Central Ltd.
- Relation
- BMC Pulmonary Medicine Vol. 15, no. 1 (2015), p. 1-11
- Rights
- Copyright © 2015 Liravi et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Rights
- Open Access
- Rights
- http://creativecommons.org/licenses/by/4.0/
- Rights
- This metadata is freely available under a CCO license
- Subject
- 1102 Cardiorespiratory Medicine and Haematology; Allergic asthma; Cytokine release; Enzyme linked immunosorbent assay; Flow cytometry; Immunohistology; Lung alveolus macrophage; Lung lavage; Lymphocyte; Molecular pathology; Protein expression; Respiratory tract inflammation
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