Allergic Rhinitis Augments Bacterial Sinusitis

过敏性鼻炎加重细菌性鼻窦炎

• 批准号: 6383672
• 负责人: ROBERT M NACLERIO
• 金额: $ 32.25万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6383672
• 关键词: Streptococcus infection; Streptococcus pneumoniae; bactericidal immunity; cellular immunity; cytokine; disease /disorder etiology; disease /disorder model; gene targeting; genetically modified animals; helper T lymphocyte; hypersensitivity; immunity; inflammation; interleukin 4; laboratory mouse; mucosal immunity; rhinitis; sinusitis

DESCRIPTION (provided by applicant): Sinusitis is a major health care problem for Americans of all ages. Despite the significant morbidity it causes and the enormous cost of managing this problem, little progress has been made at improving our basic understanding of its pathophysiology. The main constraints on the study of sinusitis have been the limited access to human sinuses and the lack of a satisfactory animal model that compares favorably with disease in man. Allergic rhinitis, a disease affecting 20 percent of Americans, is considered a major contributing factor to the development of sinusitis. We have developed a mouse model of acute sinusitis. We present data demonstrating the development of acute sinusitis in C57B1/6 and BALB/c mice after instillation ol Streptococcus pneumoniae (S. pneumoniae) (the most common pathogen responsible for acute sinusitis in man), the development of allergic rhinosinusitis in BALB/c mice, and augmentation of infection and of the inflammatory response to infection in BALB/c mice with simultaneous ongoing allergic reactions. With this model, we propose to investigate the interrelationship of allergic rhinitis and sinusitis. Our hypothesis is that the allergic response in the nose affects both the innate immune response and the host?s inflammatory response to clear the infection. Furthermore, we hypothesize that IL-4 released by Th2 cells recruited during the allergic reaction interferes with the recruitment, development, and activation of Th1 cells that contribute to the suppression of infection and inflammation caused by bacterial infection. To test these hypotheses, we propose the following specific aims. In Aim 1, we will investigate the relative importance of the innate immune system and the acquired immune system (i.e., Th1 cells) in reducing the infection arid sinus mucosal inflammation caused by intranasal inoculation of S. pneumoniae. In Aim 2, we will investigate whether Th2 cells are the component of the allergic response that leads to a more severe sinus infection after inoculation with S. pneumoniae. In Aim 3, we will investigate whether the exaggerated response to infection caused by the mucosal allergic response is due to a cytokine imbalance induced by Th2-type cytokines. By manipulating our animal model of sinusitis and exploiting the advantages of using knockout and transgenic mice, we will further increase our understanding of sinusitis and the host factors that contribute to this common disease. Our unique murine model provides the first opportunity to study this major health care problem at a level that was previously unavailable and that could lead to the identification of new treatments.

描述（由申请人提供）：鼻窦炎是一个主要的卫生保健问题 所有年龄段的美国人。尽管它引起的发病率很高， 尽管管理这一问题的成本巨大，但在这方面取得的进展甚微。 提高我们对其病理生理学的基本理解。的主要制约因素 对鼻窦炎的研究一直是有限的进入人类鼻窦和 缺乏与疾病相比有利的令人满意的动物模型， 伙计过敏性鼻炎是一种影响20%美国人的疾病， 被认为是鼻窦炎发展的主要因素。我们有 开发了一种急性鼻窦炎的小鼠模型。我们提出的数据表明， C57 B1/6和BALB/c小鼠滴注奥沙利铂后发生急性鼻窦炎 肺炎链球菌（S.肺炎）（最常见的病原体 对于急性鼻窦炎的人），过敏性鼻窦炎的发展， BALB/c小鼠，以及感染和炎症反应的增强， 感染BALB/c小鼠，同时发生过敏反应。与 这个模型，我们建议调查过敏的相互关系， 鼻炎和鼻窦炎。我们的假设是， 鼻子影响先天免疫反应和宿主？的煽动性 以清除感染。此外，我们假设IL-4释放， 在过敏反应期间募集的Th 2细胞干扰了 Th 1细胞的募集、发育和激活， 抑制由细菌感染引起的感染和炎症。到 为了验证这些假设，我们提出了以下具体目标。目标1： 将研究先天免疫系统和免疫系统的相对重要性。 获得性免疫系统（即，Th 1细胞）在减少感染和鼻窦炎中的作用 鼻内接种沙门氏菌引起的粘膜炎症。肺炎。在Aim中 2、研究Th 2细胞是否是过敏性鼻炎的组成部分， 接种S. 肺炎。在目标3中，我们将研究是否夸大的反应， 由粘膜过敏反应引起的感染是由于细胞因子 Th 2型细胞因子引起的失衡。通过操纵我们的动物模型， 鼻窦炎和利用基因敲除和转基因小鼠的优势， 我们将进一步提高对鼻窦炎和宿主因素的认识 导致这种常见疾病的原因我们独特的小鼠模型提供了 第一次有机会研究这个主要的医疗保健问题， 以前没有的，这可能会导致新的识别 治疗。