EFFECTS OF HIV ON THE IMMUNE AND NEUROENDOCRINE AXIS

获得性免疫缺陷综合症（艾滋病）是一种疾病， 影响许多器官系统，特别是免疫、神经和 内分泌系统 我们实验室和其他机构最近的研究表明， 建议，监管联系通常可能存在于 同样的三个系统。 在这个项目中，我们假设 测试的是，神经内分泌激素和/或 HIV改变了淋巴细胞对这些分子的反应性 感染，这可能介导一些内分泌和 艾滋病中的免疫异常 为了深入了解 艾滋病的病理生理学和免疫功能， 神经内分泌轴，我们建议研究艾滋病毒的影响 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。 总 目的是确定艾滋病毒和/或其产物是否影响激素 由原代和培养的淋巴细胞产生，如果相同， 来自HIV感染者在疾病不同阶段的细胞类型 也同样不正常 更具体地说， T、B和巨噬细胞谱系的细胞系以及原代 外周血淋巴细胞（PBL）将用HIV或其 子组件。 免疫测定将用于测量基础和 促肾上腺皮质激素（ACTH）、内啡肽 脑啡肽和促甲状腺激素（TSH）。 修改者 这些激素的艾滋病毒将在分子水平上进行检查， 北方印迹、原位杂交中的寡核苷酸探针，或 狭缝印迹分析。 同样需要研究的是艾滋病毒， 或其组分对免疫应答的调节作用， 神经内分泌激素 HIV处理的培养细胞系和PBL 将在放射受体结合试验中进行分析， 免疫荧光以确定激素结合能力或 受体结构发生改变。 功能测定，例如 干扰素诱导、有丝分裂或腺苷酸环化酶激活 将进行评估，以确定艾滋病毒或其成分是否影响 激素调节这些功能。 最后，来自 艾滋病不同阶段的个人将接受评估， 在体外研究中发现的异常。 这些研究应 提供了新的见解，艾滋病毒感染的作用，免疫 内分泌系统上有异常的艾滋病患者， 提出新的治疗方法来控制感染或治疗 使人虚弱的系统性改变

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.