Date of Completion
Honors College Thesis
Matthew Poynter, Ph.D.
Rona Delay, Ph.D.
Allergic Asthma; Inflammation; Cytokines; Innate Immunity
The existing mouse models for allergic asthma are incapable of reproducing all of the immunogenic and physiological features of allergic asthma as seen in humans. These models can also induce some changes inconsistent with human disease. Reasons for these inconsistencies could be the amount of allergen to which the mice are exposed, the way they are exposed, and inadvertent stress brought about through animal handling. To address these issues, we attempted to create a novel mouse model of allergic asthma induction in which mice were persistently (for 6 weeks) exposed to zero, low (1μg/g), medium (10μg/g), and high (100μg/g) doses of house dust mite extract based on the Derp1 content/g inoculated into their bedding nestlets. For this model, we based the amount of allergen inoculated into the bedding on epidemiological studies, which indicate that 5.5% of children living in homes containing a concentration of 10μg Derp1/g of carpet dust are allergically sensitized to house dust mite . At the end of the exposures, airway hyperresponsiveness was assessed and immunophenotyping was performed. We found no significant differences in the methacholine hyperresponsiveness, the production of IgG1, IgE, and IgG2a, or the cytokine production between the treatment groups. Since our model did not elicit methacholine hyperresponsiveness or HDM-specific immune responses, future studies will determine whether allergen sensitization elicited through a single intranasal instillation of 1 μg HDM extract, followed by the 6-week persistent exposure to varying concentrations of HDM as described above, elicits changes consistent with those found in human allergic asthmatics.
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Kostin, Susan F., "An Improved Model of House Dust Mite Allergic Sensitization" (2016). UVM Honors College Senior Theses. 197.