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.

在过去的几十年中，食物过敏和其他过敏性的患病率一直在稳步上升美国和其他工业化国家的疾病。令人担忧的是，食物过敏最快的增长是在儿童中观察到。食物过敏的患病率在总体中为3-4％，但为6-8％在儿童中。此外，食物过敏反应的严重程度也同时增加导致更多的住院治疗。尽管认为环境因素会发挥在这种令人震惊的趋势中，特定的病因剂仍有待确定。我们最近证明了丁基氢醌（TBHQ），这是一种合成食品添加剂，存在于许多加工食品中，促进CD4 T细胞向Th2谱系的极化，这是过敏发展的关键步骤。此外，我们的初步研究表明，TBHQ以与人类暴露有关的浓度，加剧动物模型中的食物过敏，这表明TBHQ在增加患病率中的潜在作用人类的食物过敏。对于这些研究，我们利用了不含辅助的食物过敏的独特模型并且不需要注射。这些动物通过透皮施用对食物过敏原敏感，这导致血浆IgE和IgG1水平迅速升高，即与过敏反应相关的抗体。这是值得注意的是，婴儿和幼儿也可能通过长时间对食物过敏素敏感皮肤通过尿布佩戴与食物蛋白接触。我们初步研究的关键局限性是他们是在成年动物中进行的，而食物过敏的患病率最高。所以，该提案的主要目标是确定TBHQ对食物过敏原的免疫反应的影响少年动物。我们的中心假设是合成食品添加剂TBHQ增加了IgE/IgG1的产生并加剧了少年动物的过敏反应，以响应食物过敏原。该假设基于我们强大的初步数据表明，成年小鼠暴露于低剂量的TBHQ相当于人类饮食对食物过敏原有明显增加的免疫反应，这证明了增加 IgE和IgG1的血浆水平，响应口服挑战时体温降低，增加血浆中MMCP-1的浓度，肥大细胞脱粒增加，以及其他作用。我们建议通过1）在少年动物中开发和表征食物过敏模型的假设，2）使用该模型确定TBHQ对少年动物中食物过敏原的免疫反应的影响。