EFFECTS OF HIV ON THE IMMUNE AND NEUROENDOCRINE AXIS

获得性免疫缺陷综合征是一种疾病 影响许多器官系统，特别是免疫、紧张和 内分泌系统。我们实验室和其他机构最近的研究表明， 已经提出，通常情况下，监管之间可能存在联系 这三个相同的系统。在这个项目中，我们的假设是 测试的是神经内分泌激素和/或 HIV会改变淋巴细胞对这些分子的反应性 感染，这可能会调节一些内分泌和 艾滋病中出现的免疫异常。为了深入了解这两个 艾滋病的病理生理学与免疫系统的功能 我们建议研究神经内分泌轴对HIV的影响 感染对人群激素产生和反应的影响 在细胞和分子水平上的淋巴样细胞。这位将军 目的是确定艾滋病毒和/或其产品是否影响荷尔蒙 原代和培养的淋巴样细胞的产量，如果相同 HIV感染者在疾病不同阶段的细胞类型 都是类似的功能失调。更具体地说，培养的淋巴 T、B和巨噬细胞系细胞系以及原代 外周血淋巴细胞(PBL)将接受艾滋病毒或其治疗 子组件。免疫分析将用于测量基础和 促肾上腺皮质激素(ACTH)、内啡肽、 脑啡肽和促甲状腺激素(TSH)。更改方式 这些激素的HIV将在分子水平上进行检测，使用 Northern印迹、原位杂交中的寡核苷酸探针 缝隙印迹分析。同样需要检查的是艾滋病病毒的影响， 或其成分通过以下方式调节免疫反应 神经内分泌激素。经HIV处理的培养细胞系和PBL 将在放射受体结合分析中分析，并通过 免疫荧光以确定激素结合能力或 受体结构改变。功能分析，如 干扰素诱导、有丝分裂或腺苷环化酶激活 将被评估以确定艾滋病毒或其成分是否会影响 这些功能的荷尔蒙调节。最后，淋巴细胞来自 处于艾滋病不同阶段的个人将被评估为 在体外研究中发现的异常。这些研究应该 为艾滋病病毒感染的免疫作用提供新的见解 系统出现了与艾滋病有关的内分泌异常，并可能 建议新的治疗方法来控制感染或治疗 令人衰弱的系统性改变。

The acquired immunodeficiency syndrome (AIDS) is a disease affecting many organ systems, notably the immune, nervous and endocrine systems. Recent studies, by our laboratory and others, have suggested that a regulatory link may normally exist between these same three systems. In this project, our hypothesis to be tested is that the production of neuroendocrine hormones and/or responsiveness to these molecules by lymphocytes is altered by HIV infection and that this may mediate some of the endocrine and immune abnormalities seen in AIDS. To gain insight into both the pathophysiology of AIDS and the functioning of immune- neuroendocrine axis we propose to study the effects of HIV infection on hormone production and response in populations of lYmphoid cells at both cellular and molecular levels. The general aim is to determine if HIV and/or its products effect hormone production by primary and cultured lymphoid cells and if the same type of cells from HIV infected humans at various stages of disease are similarly dysfunctional. More specifically, cultured lymphoid cell lines of T, B, and macrophage lineage as well as primary peripheral blood lymphocytes (PBLs) will be treated with HIV or its subcomponents. Immunoassays will be used to measure basal and inducible production of corticotropin (ACTH), endorphin, enkephalins and thyroid stimulating hormone (TSH). Alterations by HIV of these hormones will be examined at the molecular level using oligonucleotide probes in Northern blot, in situ hybridization, or slot blot analyses. Also to be examined is the effect that HIV, or its components have on immune response modulation by neuroendocrine hormones. HIV treated cultured cell lines and PBLs will be analyzed in radioreceptor binding assays and by immunofluorescence to determine if hormone binding ability or receptor structure is altered. Functional assays such as interferon induction, mitogenesis, or adenylate cyclase activation will be assessed to determine if HIV or its components affect hormone modulation of these functions. Finally, lymphocytes from individuals at different stages of AIDS will be assessed for the abnormalities found in the in vitro studies. These studies should provide new insight into the role HIV infection of the immune system has on the endocrine abnormalities seen with AIDS and may suggest new therapies to either control the infection or treat the debilitating systemic alterations.