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

• 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
• 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

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症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，食物过敏上升最快的是 在儿童中观察到的。虽然食物过敏在总人口中的患病率为3-4%，但它是6-8%。 在孩子们中间。此外，食物过敏反应的严重程度也同时上升。 导致更多的人住院治疗。尽管环境因素被认为对 在这一令人震惊的趋势中扮演了重要角色，具体的致病因素(S)仍有待确定。我们最近 证明了叔丁基对苯二酚(TBHQ)，一种存在于许多加工食品中的合成食品添加剂， 促进CD4T细胞向Th2谱系的极化，这是过敏发展的关键一步。 此外，我们的初步研究表明，在与人类接触相关的浓度下， 在动物模型中加剧食物过敏，表明TBHQ在增加患病率中可能起到作用 人类对食物过敏的风险。在这些研究中，我们使用了一种独特的无佐剂食物过敏模型。 而且不需要注射。这些动物通过经皮给药对食物过敏原致敏， 这会导致血浆中与过敏反应相关的抗体IgE和IgG1水平迅速上升。它是 值得注意的是，婴儿和蹒跚学步的孩子也可能通过长时间经皮接触食物过敏原。 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他们 是在成年动物身上进行的，而食物过敏的最高流行率发生在儿童身上。因此， 这项建议的一个主要目标是确定TBHQ对小鼠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的食品添加剂TBHQ增加了IgE/IgG1的产生 并加剧幼年动物对食物过敏原的过敏反应。这一假设是基于 我们强有力的初步数据表明，暴露于低剂量TBHQ的成年小鼠相当于在 人类饮食中，对食物过敏原的免疫反应明显增强，这一点从以下几个方面得到了证明 血浆中的免疫球蛋白E和免疫球蛋白1水平升高，这是对口服挑战的体温下降幅度更大的反应 血浆中mMCP-1的浓度，肥大细胞脱颗粒增加，以及其他影响。我们建议 通过1)建立和表征幼年动物的食物过敏模型和2)使用 该模型确定了TBHQ对幼年动物对食物过敏原的免疫反应的影响。