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Interventions for primary prevention of post-bronchiolitis allergic sensitization in guinea pigs

University of British Columbia

Asthma is a serious health problem that affects over 2.4 million Canadians. Asthma and allergy are closely linked and 80% of asthmatic children are allergic to at least one inhaled antigen. Among several conditions of diverse etiology that are included in asthma, we studied postbronchiolitis asthma and allergy in children, in which an episode of acute bronchiolitis precedes the onset of asthma. By focusing on the Thl/Th2 paradigm concept, in which shifting the Thl/Th2 balance towards Th2 is characteristic of allergic responses, we proposed two types of interventions for preventing the post-bronchiolitis allergic sensitization and asthma in a guinea pig model of respiratory syncytial virus (RSV) infection and ovalbumin (OA) sensitization. These interventions, which included inoculation of animals with relatively "low doses" of RSV or administration of CpG-ODN (synthetic oligodeoxynucleotides rich in cytosine and guanine) before experimental RSV infection plus OA exposures, were applied to shift the Thl/Th2 towards Thl responses. We compared 4 groups of animals (n=10-12/group), including controls and animals that had the intervention. We compared airway inflammatory cells (eosinophils and T cells) by point counting of the Hansel stained and anti-CD3 immunostained formalin-fixed paraffin embedded lung sections. Using ELISA, we also measured the titers of serum OAspecific IgGi antibodies, which increase during allergic sensitization and reflect Th2 responses. We also compared lung IFNy/IL-5 gene expression ratios as indices of Thl/Th2 balance, by semi-quantitative RT-PCR method. The results showed that low dose RSV had no effect on any of the indices of allergy and asthma examined. However, CpG-ODN intervention decreased the percentage of inflammatory cells and the titers of IgGi antibodies, and increased the lung IFNy/IL-5 gene expression ratios. We also tested the effect of CpG-ODN on uninfected OAsensitized guinea pigs and the results showed that CpG-ODN did not affect OA sensitization. In conclusion, the "low dose" RSV intervention had no effect on post-bronchiolitis allergic sensitization of guinea pigs but the CpG-ODN administration provided partial protection against combination of RSV infection and OA sensitization.

Thesis/Dissertation

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2009-11-03

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http://hdl.handle.net/2429/14646

Experimental Medicine

University of British Columbia

UBCV

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