CLINICAL INVESTIGATIONS IN LUNG HOST DEFENSES

肺宿主防御的临床研究

• 批准号: 6183217
• 负责人: Neil W. Schluger
• 金额: $ 11.27万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-20 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6183217
• 关键词: aerosols; antigen presenting cell; bactericidal immunity; chemokine; clinical research; enzyme linked immunosorbent assay; flow cytometry; host organism interaction; human subject; human therapy evaluation; immunotherapy; inhalation drug administration; interferon gamma; leukocyte activation /transformation; outcomes research; respiratory disease /disorder therapy; tuberculosis

Tuberculosis remains the world's leading infectious cause of death, and the rise of multidrug resistant tuberculosis and the interaction of the TB and AIDS epidemics worldwide are creating a public health threat of massive proportions. In recent years, we have pursued studies aimed at elucidating ways in which the host immune response to tuberculosis may offer protection from the disease, as well as ways in which inflammatory responses can be modified to improve outcomes in patients with multidrug resistant tuberculosis. We have demonstrated that the cytokine interferon (IFN) gamma plays a major role in human host defense against tuberculosis; a detailed understanding of immune mechanisms upstream and downstream from IFN's action in patients should provide significant insight into protection against tuberculosis infection and disease. To that end, three specific aims are planned: Specific aim 1: To assess, by determining the types and levels of chemokine present in bronchoalveolar lavage fluid of patients with tuberculosis, the signals in the lung which may cause recruitment of immune effector cells associated with an effective host response. Specific aim 2: To assess the state of activation of antigen presenting cell as well as immune effector cells in the lungs of patients with tuberculosis compared to controls. Specific aim 3: To assess changes in the pulmonary host response after administration of interferon gamma by aerosol to clearly define the mechanisms by which IFN causes clinical improvement in tuberculosis patients.

结核病仍然是世界上最主要的传染病死亡原因，耐多药结核病的兴起以及全世界结核病和艾滋病流行的相互作用正在对公共卫生造成巨大威胁。 近年来，我们进行了一系列研究，旨在阐明宿主对结核病的免疫反应可以提供针对该疾病的保护作用，以及可以改变炎症反应以改善耐多药结核病患者的预后的方法。 我们已经证明，细胞因子干扰素 (IFN) γ 在人类宿主防御结核病方面发挥着重要作用；详细了解干扰素在患者体内作用的上游和下游免疫机制，将为预防结核感染和疾病提供重要的见解。 为此，计划了三个具体目标： 具体目标 1：通过确定结核病患者支气管肺泡灌洗液中存在的趋化因子的类型和水平，评估肺部中可能导致与肺结核相关的免疫效应细胞募集的信号。有效的宿主响应。 具体目标 2：与对照组相比，评估结核病患者肺部抗原呈递细胞和免疫效应细胞的激活状态。 具体目标 3：评估通过气雾剂施用干扰素 γ 后肺部宿主反应的变化，以明确 IFN 导致结核病患者临床改善的机制。