ALLERGEN, NEUROGENIC INFLAMMATION AND CHRONIC SINUSITIS

过敏原、神经源性炎症和慢性鼻窦炎

• 批准号: 6099870
• 负责人: Alkis Togias
• 金额: $ 16.27万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6099870
• 关键词: allergens; biopsy; calcitonin gene related peptide; capsaicin; chronic disease /disorder; colony stimulating factor; exopeptidase; glucocorticoids; histamine; human subject; immunocytochemistry; in situ hybridization; interleukin 6; interleukin 8; ion transport; membrane potentials; methacholine; neurophysiology; olfactions; radioimmunoassay; respiratory epithelium; respiratory hypersensitivity; sinusitis; substance P; vasoactive intestinal peptide

This project will begin to investigate how allergic rhinitis may contribute to the pathophysiology of chronic sinusitis by examining the relationship between allergic rhinitis, neuronal reflexes and sinusitis. Our central hypothesis is that allergic inflammation in the nasal cavity stimulates sensory nerves that, through centrally mediated and axonal reflexes, affect epithelial function within the sinuses. The induced neurogenic inflammation, in turn, stimulates sensory nerves within the sinuses to initiate central reflexes that stimulate the nasal mucosa, creating a viscious cycle. We will study allergic and nonallergic subjects with and without chronic sinusitis to test several aspects of this hypothesis. We will monitor epithelial function by measuring cytokine production in secretions and in tissue, epithelial potential difference and evidence of changes in secretory and vascular function. In Aim 1, we will extend our observations on central nasonasal, reflex- induced glandular stimulation by testing whether neuronal reflexes alter epithelial ion and water transport and stimulate cytokine (IL-6, IL-8 and GM-CSF) generation by epithelial cells. Local anesthetics will be used to reduce neuronal transmission. Allergic subjects will be challenged with allergen, while both allergic and nonallergic subjects will be challenged with nonantigenic stimuli (bradykinin, histamine, capsaicin and methacholine). We will also compare neuronal responses in allergic subjects with and without sinusitis. In Aim 2, we will extend our studies to sinusitis patients who have undergone surgical intervention because, in these subjects, the sinus mucosa is readily accessible. This will allow us to directly measure whether neurogenic inflammation can be elicited in the ipsi- and contralateral sinuses in responses to antigenic and nonantigenic stimulation of the nasal mucosa. In Aim 3, we will determine whether intranasal glucocorticoid therapy prevents alterations of epithelial ion transport and epithelial cytokine production, induced by neuronal reflexes. In Aim 4, we will determine the answer to three related questions. First, does activation of sensory nerves within the sinuses induce reflexes with the nasal cavity? Second, since, postoperatively, the sinuses become directly accessible to environmental influences, does the inflammatory response to allergic stimulation of the sinuses mimic the responses seen in the nasal mucosa? Third, if our central hypothesis is correct, does reduction of inflammation within the sinus cavity by surgical intervention reduce nasal responsiveness? Throughout this project, we will test whether allergic subjects with asthma respond differently than allergic subjects without this condition. This project depends upon the Core for subjects and interrelates strongly with Project 2, which examines epithelial cell cytokine production in response to viral infection, and Project 3, which examines epithelial ion transport in vitro and in vivo.

该项目将开始调查如何过敏性鼻炎可能 有助于慢性鼻窦炎的病理生理学检查， 变应性鼻炎、神经反射与鼻窦炎的关系 我们的中心假设是鼻腔的过敏性炎症 刺激感觉神经，通过中枢介导和轴突 反射，影响鼻窦内的上皮功能。 感应 神经源性炎症，反过来，刺激感觉神经内的 鼻窦启动刺激鼻粘膜的中枢反射， 形成一个粘性循环。 我们将研究过敏和非过敏 受试者与非慢性鼻窦炎测试的几个方面， 这个假设。 我们将通过测量 分泌物和组织中细胞因子的产生，上皮细胞潜能 分泌和血管功能变化的差异和证据。 在 目的1，我们将扩大我们的观察中枢鼻，反射- 通过测试神经元反射是否改变 上皮细胞离子和水转运并刺激细胞因子（IL-6、IL-8和 GM-CSF）产生。 局部麻醉剂将用于 减少神经传递。 过敏受试者将接受以下挑战： 过敏原，而过敏和非过敏受试者都将受到挑战 与非抗原性刺激（缓激肽，组胺，辣椒素和 乙酰甲胆碱）。 我们还将比较过敏反应中的神经元反应， 有和没有鼻窦炎的受试者。 在目标2中，我们将扩展我们的研究 鼻窦炎患者谁经历了手术干预，因为， 在这些受试者中，窦粘膜易于接近。 这将允许 我们直接测量是否可以引起神经源性炎症， 同侧和对侧鼻窦对抗原和 鼻粘膜的非抗原性刺激。 在目标3中，我们将确定 鼻内糖皮质激素治疗是否能阻止 上皮细胞离子转运和上皮细胞因子的产生，由 神经反射 在目标4中，我们将确定三个问题的答案 相关问题。 首先，大脑皮层内感觉神经的激活 鼻窦会引起鼻腔反射吗 其次，由于， 手术后，鼻窦可以直接接触到环境 影响，对过敏性刺激的炎症反应， 鼻窦模仿鼻粘膜的反应？ 第三，如果我们 中心假设是正确的，减少炎症内 鼻窦手术干预降低鼻腔反应性？ 在整个项目中，我们将测试过敏受试者是否患有 哮喘的反应不同于没有这种情况的过敏性受试者。 这个项目依赖于核心的主题和强烈的相互关联 与项目2，检查上皮细胞细胞因子的生产， 对病毒感染的反应，以及项目3，检查上皮细胞离子 体外和体内转运。