Severe asthma and viral-induced asthma exacerbations represent a high unmet medical need as no therapy is currently available for these patients. HRV (human rhinovirus) is prominently associated with asthma exacerbations in humans. The aim of the present study was to establish a mouse model of severe asthma with additional rhinovirus infection to investigate the interplay between chronic allergic airway inflammation and acute respiratory viral infection. Balb/c mice were sensitized with HDM (house dust mite) extract (25 μg in 50 μl of saline) by i.n. (intranasal) delivery to the lung over 7 weeks. HRV1B (HRV serotype 1B) inoculation was performed i.n. on the last 3 days. Therapeutic treatment with FP (fluticasone propionate) was performed to assess steroid efficacy. Lung resistance was measured invasively to assess AHR (airway hyper-responsiveness). BAL (bronchoalveolar lavage) differential cell count, cytokines, lung histology and the proliferative and cytokine response of MLN (mediastinal lymph node) cells upon in vitro restimulation were analysed. Chronic HDM application induced a strong Th2-skewed eosinophilic airway inflammation and AHR, which was not exacerbated by superimposed HRV1B infection. Therapeutic steroid intervention in the chronic HDM model reduced BAL eosinophil cell counts, cytokine levels and AHR, while neutrophil numbers were unaffected. Steroid efficacy against inflammatory readouts was maintained during additional HRV1B infection. Animals with chronic allergic airway inflammation exhibited a diminished immune response towards superimposed HRV1B infection compared with HRV1B alone, as induction of the anti-viral and pro-inflammatory cytokines IFN (interferon)-α, IFN-γ and IL (interleukin)-12 were suppressed. Although superimposed HRV1B infection did not provoke asthma exacerbation in this severe model, a deficient anti-viral immune response to HRV1B was present under chronic allergic airway inflammatory conditions. Thus, this model is able to reflect some aspects of the complex interplay of respiratory virus infection in chronic allergic asthma.
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Research Article|
September 03 2013
No exacerbation but impaired anti-viral mechanisms in a rhinovirus-chronic allergic asthma mouse model
Sabine Rochlitzer;
Sabine Rochlitzer
*Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany
†Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Germany
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Heinz-Gerd Hoymann;
Heinz-Gerd Hoymann
*Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany
†Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Germany
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Meike Müller;
Meike Müller
*Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany
†Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Germany
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Armin Braun
on behalf of the U-BIOPRED consortium
*Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany
†Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Germany
Correspondence: Professor Armin Braun (email [email protected]).
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Publisher: Portland Press Ltd
Received:
March 28 2013
Revision Received:
June 26 2013
Accepted:
July 03 2013
Accepted Manuscript online:
July 03 2013
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 126 (1): 55–65.
Article history
Received:
March 28 2013
Revision Received:
June 26 2013
Accepted:
July 03 2013
Accepted Manuscript online:
July 03 2013
Citation
Sabine Rochlitzer, Heinz-Gerd Hoymann, Meike Müller, Armin Braun; on behalf of the U-BIOPRED consortium, No exacerbation but impaired anti-viral mechanisms in a rhinovirus-chronic allergic asthma mouse model. Clin Sci (Lond) 1 January 2014; 126 (1): 55–65. doi: https://doi.org/10.1042/CS20130174
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