Optimizing the dose-response of Interleukin-4 (IL-4) to further investigate its role in the association between Maternal Allergic Asthma and Neurodevelopmental Disorders.
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Abstract
Clinical studies have demonstrated that allergic asthma during pregnancy is linked to an increased risk of neurodevelopmental and neuropsychiatric disorders in offspring. The Schwartzer Lab has developed a Maternal Allergic Asthma (MAA) model that has established a role for Interleukin-4 (IL-4) connecting MAA to neurodevelopmental deficits in the offspring. A forthcoming research project will examine the sufficiency of IL-4 by evaluating whether elevations in maternal IL-4 dosage have a dose-dependent effect on offspring behavioral deficits. However, it remains unknown the appropriate IL-4 dosage to be administered in a mouse model to replicate the IL-4 response observed in MAA. The goal of this research is to identify the optimal IL-4 dosage needed to mimic the inflammatory responses observed in MAA. To test this, Experiment 1 investigated the best time to take blood samples from female C57 mice when exposed to OVA and when injected with 5μg of IL-4. In Experiment 2, we aimed to investigate the IL-4 dose response by injecting 2 different doses of IL-4 in the mice. In both experiments, blood samples were analyzed using Bead-Based immunoassays to measure IL-4 biomarker concentrations. Findings show that IL-4 IP injection has a higher rate of decay post-exposure, when compared to MAA OVA exposure. We also estimate an IL-4 dose of 0.025 ug suitable for IP injection in a mouse model aimed at investigating the cytokine’s sufficiency in causing neurodevelopmental disorders in the offspring. This thesis research project was positioned to derive an IL-4 dose-response curve, thereby providing guidance in determining the optimal injection dosage for future studies exploring the causal link between maternal IL-4 and MAA.
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Maternal Allergic Asthma, Pharmacokinetics, Interleukin-4 (IL-4), Dose Response, Mouse Model, Neurodevelopmental Disorders