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Viral infection in a murine model of allergic airways inflammation: actions of corticosteroids

Cholisoh, Zakky 2014. Viral infection in a murine model of allergic airways inflammation: actions of corticosteroids. PhD Thesis, Cardiff University.
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Viral respiratory infection exacerbates asthma symptoms in almost all patients with allergic asthma. Asthma symptoms in viral associated asthma exacerbation are often severe and require urgent care as well as hospitalisation. Corticosteroids are the mainstay treatment for asthma. However, they are less effective in treating virus associated asthma exacerbation. The main aim of the thesis is to determine the role of virus infection in airway allergic inflammation and then define the effects of corticosteroids in virus associated exacerbations of airway allergic inflammation. Mice sensitised and challenged with ovalbumin demonstrated most of the main features of asthma including lung cellular inflammation with eosinophilia, early phase asthmatic responses (EAR), late phase asthmatic responses (LAR), and airway hyperresponsiveness (AHR) to methacholine provocations. Treatment with either systemic (dexamethasone: DEX) or inhaled (fluticasone propionate: FP) corticosteroids in the murine ovalbumin allergic airways inflammation model attenuated inflammatory cells influx and eosinophilia, LAR, and the AHR. Influenza A (H1N1/PR8) is the most infective to mice compared to human parainfluenza virus type 3 (HPIV3), and a synthetic dsRNA, poly (I:C). Influenza infection in mice caused a significant increase of inflammatory cell influx in the airways with marked neutrophilia, and AHR. Ovalbumin challenge in the acute course of influenza infection on a murine model of allergic airways inflammation exacerbated the inflammatory cells influx, LAR, and AHR. Treatment with either DEX or FP attenuated the airway cellular inflammation, LAR, but not the AHR. Mice only infected with influenza were resistant to the corticosteroids (DEX and FP) treatment. DEX but not FP showed antiviral activity against HPIV3 and influenza A in vitro. These data suggest that influenza infection in a murine model of allergic airways inflammation exacerbates the inflammation and alters the sensitivity toward corticosteroids. It is also suggested that some elements in the influenza associated exacerbation of murine model of allergic airways inflammation are refractory or not regulated by corticosteroid treatment.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Airways inflammation, Asthma, Ovalbumin, Mouse model, Virus infection, Corticosteroid
Date of First Compliant Deposit: 30 March 2016
Last Modified: 19 Mar 2016 23:37

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