BOVINE IGG AND INFANT COLIC

牛 IGG 和婴儿绞痛

基本信息

批准号：
2378524
负责人：
ANTHONY KULCZYCKI
金额：
$ 17.66万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-01-01 至 1999-02-28
项目状态：
已结题

项目摘要

Infant colic is a pediatric disorder of unknown etiology. Colic is characterized by excessive crying and it affects 20% of U.S. infants, whether breast-fed or formula-fed. Colic is important because of infant pain, parental frustration with inconsolable crying, some infant abuse mortality, pediatrician effort, expense, and lack of effective treatment. Since levels of bovine IgG (BGG) in infant formulas and human milk are comparable, and breast milk BGG levels seems to correlated with colic, an investigation of whether dietary BGG might be a major cause of colic is proposed. BGG is the major foreign immunoglobulin in the human diet (often 500 mg/day) and has unique properties of intentional transport, stability, binding to Fc receptors, and immunomodulation. In vitro studies suggest that BGG may profoundly influence the developing mucosal immune system and might initiate colic and certain inflammatory diseases. As one immediate goal, this hypothesis will be tested directly by conducting double-blind placebo-controlled trials comparing infant responses after ingestion of BGG and placebo. Both breast-fed infants and formula-fed infants will be tested and colic responses will be assessed by simplified cry diaries. The effect of maternal consumption of diary products on breast milk levels of BGG and on colic in breast-fed infants will also be studied. Since preliminary data show elevated levels of serum BGG in patients with various forms of colitis, a second goal is to determine whether BGG plays an important role in milk-induced colitis, ulcerative colitis, and eosinophilic gastroenteritis. This will be carried out by analyzing sera of patients during exacerbations of these disorders for levels of BGG will be assessed by RAST assay. Another goal is to better understand how BGG is selectively transported and how BGG may cause colic or other diseases in susceptible individuals. Whether intestinal FcR account for selective BGG absorption will be studied in an animal model using a FcR-deficient mouse strain. How and when selective BGG transport occurs i humans will be investigated by measuring milk and serum levels of BGG at various stages of pregnancy and lactation. A knowledge of the role of ingested bovine IgG in colic and other disorders may lead to better methods of prevention and treatment. This research might also provide insights into etiology of autoimmune diseases (rheumatoid arthritis, Type I diabetes).

婴儿绞痛是一种未知病因的儿科疾病。绞痛是以过度哭泣为特征，它影响了20％的美国婴儿无论是母乳喂养还是配方奶粉。绞痛很重要，因为婴儿痛苦，父母沮丧，无法哭泣，一些婴儿虐待死亡率，儿科努力，费用和缺乏有效治疗。由于婴儿配方和人乳中的牛IgG（BGG）水平是可比，母乳BGG水平似乎与绞痛相关，对饮食BGG是否可能是绞痛的主要原因的调查提出了。 BGG是人类饮食中主要的外国免疫球蛋白（通常为500毫克/天），并且具有故意运输的独特特性，稳定性，与FC受体结合以及免疫调节。体外研究表明，BGG可能会深刻影响发展中的粘膜免疫系统，可能引发绞痛和某些炎症性疾病。作为一个直接目标，该假设将直接通过进行双盲安慰剂对照试验比较婴儿摄入BGG和安慰剂后的反应。两个母乳喂养的婴儿将测试配方奶粉的婴儿，绞痛反应将是通过简化的哭泣日记进行评估。孕产妇消费的影响母乳的母乳和绞痛上的日记产物的母乳喂养婴儿也将被研究。由于初步数据显示了各种形式的结肠炎患者的血清BGG水平，第二目标是确定BGG在牛奶引起的结肠炎，溃疡性结肠炎和嗜酸性胃肠炎。这会通过分析患者的血清在恶化期间进行这些针对BGG水平的疾病将通过RAST分析评估。另一个目标是更好地了解如何选择性地运输BGG 以及BGG如何在易感人群中引起绞痛或其他疾病。肠道FCR是否为选择性BGG的吸收是使用FCR缺陷小鼠菌株在动物模型中进行了研究。如何和当有选择性的BGG运输发生时，我将对人类进行调查在怀孕的各个阶段测量牛奶和血清水平哺乳。了解摄入的牛IgG在绞痛中的作用其他疾病可能会导致更好的预防和治疗方法。这项研究还可能提供对自身免疫性病因的见解疾病（类风湿关节炎，I型糖尿病）。