CYTOKINES AND ANTIGEN-INDUCED AIRWAY HYPERREACTIVITY

细胞因子和抗原诱导的气道高反应性

• 批准号: 2027690
• 负责人: DANIEL J O'HEARN
• 金额: $ 3.25万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-12-28 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2027690
• 关键词: immunoregulation; interleukin 12; interleukin 4; respiratory hypersensitivity

ABergic asthma is characterized by airway inflammation and hyperreactivity upon exposure to allergens. Although the etiology of this disease is unknown, studies have shown an association of activated T lymphocytes in human asthma. Two distinct sets of CD4+ T cells have been described; Th2 cells produce Interleukin-4 (IL-4) and IL-5 whereas Th1 cells produce IL-2 and Interferon-gamma. IL-4 and IL-5 are important in the IgE response and eosinophilia, respectively. We have described a murine model in which inbred strains of mice develop many of the characteristics of allergic asthma following antigen-challenge, that is, airway hyperreactivity and eosinophilic inflammation; other murine strains do not develop such responses. We have shown that the allergic response of susceptible mice is CD4+ T cell-dependent and is associated with increases in IL-4 and IL-5. The overall hypothesis of this proposal is that the Th2 cytokine pattern is responsible for the airway inflammation anhyperreactivity following antigen exposure in susceptible mice. First, we will compare the lung cytokine profiles of susceptible and resistant mice after exposure to antigen and determine the cellular source of these cytokines. Second, we will examine the immunoregulatory roles of IL-4 and IL-12. These experiments should bring further insight into the immunologic basis of airway inflammation and hyperreactivity and should provide a unique opportunity to begin determining the pathogenesis of asthma.

ABERGIC哮喘的特征是气道炎症和 暴露于过敏原时过度反应性。虽然这个病因 疾病尚不清楚，研究表明活化的T 人哮喘中的淋巴细胞。两组CD4+ T细胞已经 描述； Th2细胞产生白介素-4（IL-4）和IL-5，而Th1 细胞产生IL-2和干扰素 - 伽马。 IL-4和IL-5在 IgE反应和嗜酸性粒细胞分别。我们已经描述了一个 鼠模型，其中近交菌株的小鼠发展了许多 抗原挑战后的过敏性哮喘的特征，也就是说 气道高反应性和嗜酸性炎症；其他鼠 菌株不会产生这种反应。我们已经证明了过敏性 易感小鼠的响应是CD4+ T细胞依赖性的，并且是相关的 随着IL-4和IL-5的增加。该提议的总体假设 是Th2细胞因子模式是导致气道的原因 抗原暴露后的炎症无反应性 老鼠。首先，我们将比较易感的肺细胞因子特征 暴露于抗原后的耐药小鼠并确定细胞 这些细胞因子的来源。其次，我们将检查免疫调节性 IL-4和IL-12的作用。这些实验应带来进一步的见识 进入气道炎症和过度反应性的免疫学基础 应该提供一个独特的机会开始确定发病机理 哮喘。