LYMPHOCYTIC ALVEOLITIS, IL 1B REGULATION AND LUNG INJURY

描述（改编自申请人摘要） 有几条证据支持这样一个概念， 在肺实质中发生大量的艾滋病毒- 血清反应阳性的个人之前，发展公认的 肺部并发症 虽然这些疾病的发病机制 异常仍然模糊，最近的证据表明， HIV相关淋巴细胞性肺泡炎的重要作用和关键 肺泡淋巴细胞-肺泡巨噬细胞相互作用。 的目标 目前的项目是通过严格检查这些观察结果 淋巴细胞性肺泡炎的意义 肺损伤的生理和形态学证据以及 关于肺泡巨噬细胞产生细胞因子的失调。 为实现这一目标，将审查以下具体目标 目标. 具体目标1解决了这个问题： HIV相关的淋巴细胞性肺泡炎是 实质性肺损伤和促炎细胞因子上调？ 这 目的是前瞻性地描述淋巴细胞的重要性， 肺泡炎的生理、影像学和形态测量学 实质性肺损伤的证据以及体内 促炎细胞因子诱导。 具体目标2 地址：是在体外存在肺泡细胞毒性T淋巴细胞 TNF α和IL-1产生中的重要调节因子 肺泡巨噬细胞释放β-肾上腺素 这一目标将审查的基本机制， 促炎细胞因子调节，并将主要集中在 CD 8+细胞毒性淋巴细胞对IL-β加工和释放的影响 被肺泡巨噬细胞吞噬 因为这项研究强调了 最常见的炎症事件之一， 肺泡环境中的艾滋病毒，它可能会大大推进艾滋病毒的知识- 相关的肺病。 也许更重要的是，它关注的是 肺泡淋巴细胞作为一个中心参与者 通过与肺泡相互作用的肺实质损害 巨噬细胞 因此，该项目提供了一个机会， 阐明肺损伤的新机制， 对监管具有潜在根本重要性的因素 炎症

DESCRIPTION (Adapted from the applicant's abstract) Several lines of evidence support the concept that important alterations in the pulmonary parenchyma occur in a substantial number of HIV- seropositive individuals prior to the development of recognized pulmonary complications. Although the pathogenesis of these abnormalities remains obscure, recent evidence has suggested an important role for an HIV-associated lymphocytic alveolitis and critical alveolar lymphocyte-alveolar macrophage interactions. The goal of the present project is to extend these observations by rigorously examining the significance of a lymphocytic alveolitis both with respect to physiologic and morphologic evidence of lung injury as well as with respect to dysregulation of cytokine production by alveolar macrophages. The following specific aims will be examined in an effort to reach this goal. Specific Aim 1 addresses this question: Is the in vivo presence of an HIV-associated lymphocytic alveolitis a critical determinant of parenchymal lung injury and proinflammatory cytokine upregulation? This aim will prospectively delineate the importance of a lymphocytic alveolitis with respect to physiologic, radiographic, and morphometric evidence of parenchymal lung damage as well as with respect to in vivo proinflammatory cytokine induction. The question in Specific Aim 2 addresses: Is the in vitro presence of alveolar cytoxic T- lymphocytes an important regulatory factor in the production of TNF alpha and IL-1 beta by alveolar macrophages? This aim will examine basic mechanisms of proinflammatory cytokine regulation and will focus primarily on the effects of CD8+ cytotoxic lymphocytes on IL-beta processing and release by alveolar macrophages. Because this study addresses the significance of one of the most common of the inflammatory events occurring in the alveolar environment in HIV, it may greatly advance knowledge of HIV- related lung disease. Perhaps more importantly, it focuses on the role of the alveolar lymphocyte as a central player in orchestrating pulmonary parenchymal damage through interactions with alveolar macrophages. As such, this project represents an opportunity to elucidate novel mechanisms of lung injury and to better understand factors of potentially fundamental importance to the regulation of inflammation.