The effect of the synthetic food additive tBHQ on food allergy in juvenile animals

合成食品添加剂tBHQ对幼年动物食物过敏的影响

基本信息

批准号：
9807714
负责人：
Cheryl Elizabeth Rockwell
金额：
$ 7.83万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-17 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9807714
关键词：
2-tert-butylhydroquinone Adjuvant Adolescent Adult Age Allergens Allergic Disease Anaphylaxis Animal Model Animals Antibodies Antibody Formation Asthma Body Temperature CD4 Positive T Lymphocytes Cell Degranulation Child Cholera Toxin Clinical Data Developed Countries Development Diet Disease Dose Drops Eating Environmental Impact Environmental Risk Factor Experimental Models Exposure to Food Food Additives Food Hypersensitivity Goals High Prevalence Hospitalization Human Hypersensitivity IgE IgG1 Immune response Immune system Incidence Infant Injections Mediating Modeling Mus Oral Ovalbumin Phase Physiological Plasma Play Population Prevalence Process Production Proteins Reaction Risk Role Severities Skin Solid T-Lymphocyte Testing Toddler Transdermal substance administration allergic response base environmental chemical exposed human population food allergen intraperitoneal juvenile animal mast cell mature animal oral tolerance prevent pup response trend

项目摘要

Over the last several decades, there has been a steady rise in the prevalence of food allergy and other allergic diseases in the U.S. and other industrialized countries. Of concern, the most rapid rise in food allergy has been observed in children. Whereas the prevalence of food allergy is 3-4% in the overall population, it is 6-8% among children. In addition, there has also been a concurrent rise in the severity of food allergy reactions resulting in a greater number of hospitalizations. Although environmental factors are thought to play a significant role in this alarming trend, the specific causative agent(s) remain to be identified. We recently demonstrated that tert-butylhydroquinone (tBHQ), a synthetic food additive present in many processed foods, promotes polarization of CD4 T cells towards the Th2 lineage, a key step in the development of allergy. Furthermore, our preliminary studies demonstrate that tBHQ, at concentrations relevant to human exposure, exacerbates food allergy in an animal model, suggesting a potential role for tBHQ in the increased prevalence of food allergy in humans. For these studies, we utilized a unique model of food allergy that is adjuvant-free and does not require injections. The animals are sensitized to food allergen via transdermal administration, which results in a rapid rise in plasma levels of IgE and IgG1, antibodies associated with allergic response. It is worth noting that infants and toddlers may also be sensitized to food allergen transdermally through prolonged skin contact to food proteins through diaper wearing. A key limitation of our preliminary studies is that they were conducted in adult animals, whereas the highest prevalence of food allergy occurs in children. Therefore, a major goal of this proposal is to determine the effect of tBHQ on the immune response to food allergen in juvenile animals. Our central hypothesis is that the synthetic food additive tBHQ increases IgE/IgG1 production and exacerbates anaphylaxis in juvenile animals in response to food allergen. This hypothesis is based upon our strong preliminary data showing that adult mice exposed to a low dose of tBHQ equivalent to that found in the human diet, have a markedly increased immune response to food allergen, as evidenced by increased plasma levels of IgE and IgG1, greater decrease in body temperature in response to oral challenge, increased concentrations of mMCP-1 in plasma, increased mast cell degranulation, among other effects. We propose to test our hypothesis by 1) developing and characterizing a model of food allergy in juvenile animals and 2) using that model to determine the effect of tBHQ on the immune response to food allergen in juvenile animals.

在过去的几十年里，食物过敏和其他过敏性疾病的患病率稳步上升美国和其他工业化国家的疾病。值得关注的是，食物过敏上升最快的是在儿童中观察到。总体人口中食物过敏的患病率为 3-4%，而这一比例为 6-8% 儿童之间。此外，食物过敏反应的严重程度也同时上升导致住院人数增加。尽管环境因素被认为发挥着影响尽管在这一令人震惊的趋势中发挥了重要作用，但具体的致病因素仍有待确定。我们最近证明叔丁基氢醌（tBHQ）是一种存在于许多加工食品中的合成食品添加剂，促进 CD4 T 细胞向 Th2 谱系极化，这是过敏发展的关键一步。此外，我们的初步研究表明，tBHQ 在与人体暴露相关的浓度下，加剧动物模型中的食物过敏，表明 tBHQ 在患病率增加中具有潜在作用人类食物过敏。在这些研究中，我们使用了一种独特的不含佐剂的食物过敏模型并且不需要注射。通过透皮给药使动物对食物过敏原敏感，这会导致血浆 IgE 和 IgG1（与过敏反应相关的抗体）水平迅速上升。这是值得注意的是，婴儿和幼儿也可能通过长时间的经皮接触而对食物过敏原敏感。皮肤通过穿尿布接触食物蛋白质。我们初步研究的一个关键限制是它们是在成年动物中进行的，而食物过敏的发病率最高发生在儿童身上。所以，该提案的一个主要目标是确定 tBHQ 对食物过敏原免疫反应的影响幼年动物。我们的中心假设是合成食品添加剂 tBHQ 会增加 IgE/IgG1 的产生并加剧幼年动物对食物过敏原的过敏反应。这个假设是基于我们强有力的初步数据表明，成年小鼠暴露于低剂量的 tBHQ，相当于在人类饮食中，对食物过敏原的免疫反应显着增强，这一点可以通过增加血浆 IgE 和 IgG1 水平，口服刺激后体温下降幅度更大，增加血浆中 mMCP-1 的浓度、增加肥大细胞脱颗粒等效应。我们建议通过 1) 开发和表征幼年动物食物过敏模型以及 2) 使用该模型旨在确定 tBHQ 对幼年动物食物过敏原免疫反应的影响。