PATHOGENESIS AND CYTOKINES IN HIV SENSORY NEUROPATHY

中枢神经系统、外周神经系统和免疫系统 人类免疫缺陷病毒1型（HIV-1）感染的主要目标 获得性免疫缺陷综合征（AIDS）患者的免疫功能。 的 周围神经病变的发病机制尚未阐明。 的 外周感觉系统的结构特征提供了 确定神经元损伤的确切机制的可能性是 产生的HIV-1，解剖出相关的作用， 巨噬细胞/单核细胞，HIV-1感染-巨噬细胞/单核细胞，细胞因子 生产和机会性病毒感染。 我们将检验远端进行性感觉 艾滋病的神经病变是1）一种垂死的背部疾病，2） 由巨噬细胞分泌的因子或细胞因子是可能的原因。 我们 将使用免疫组织化学、PCR技术和原位杂交 为了鉴定外周神经组织中的胆碱产生细胞， 确认艾滋病患者体内HIV-1感染细胞的身份， 机会性病毒的存在。 细胞因子的产生将是 与炎症、神经元损失和HIV-1复制相关。 艾滋病死亡患者的腓肠神经和死后组织活检 急性死亡对照包括腓肠、胫骨和坐骨神经 神经，相应的L5和S1背根神经节，以及整个 脊髓 将进行形态测定分析，以确定这是否 是一个真正的垂死回神经病变或由于累积效应， 多发性周围神经损伤 这项提案利用了 死于艾滋病的受试者中神经病变的发生率， 确定神经病变的发生率和进展是否在 AIDS受试者可由细胞因子产生引起， 巨噬细胞/单核细胞在DRG中原位。

The central and peripheral nervous system and the immune system are primary targets for human immunodeficiency virus type 1 (HIV-1) infection in individuals with acquired immunodeficiency syndrome (AIDS). The pathogenesis of the peripheral neuropathy has not been elucidated. The structural features of the peripheral sensory system offers the possibility to determine the exact mechanism by which neuronal damage is produced by HIV-1, dissecting out the relevant roles of macrophage/monocytes, HIV-1 infection-of macrophage/monocytes, cytokines production, and opportunistic viral infections. We will test the hypotheses that the distal progressive sensory neuropathy of AIDS is 1) A dying back disorder and 2) that humoral factors or cytokines secreted by macrophages are the likely cause. We will use immunohistochemistry, PCR techniques and in situ hybridization to identify cytokine-producing cells in peripheral nervous tissue from AIDS patients to confirm the identity of the HIV-1 infected cells, and the presence of opportunistic viruses. Cytokine production will be correlated with inflammation, neuronal loss, and replication of HIV-1. Biopsied sural nerve and post-mortem tissues of patients dying with AIDS and acute death controls will include the sural, tibial and sciatic nerves, the corresponding L5 and Sl dorsal root ganglia, and the whole spinal cord. Morphometric analyses will be performed to decide if this is a true dying back neuropathy or due to the cumulative effects of multiple peripheral nerve lesions. This proposal capitalizes on the high incidence of neuropathy among subjects dying with AIDS and will result in determination whether the incidence and progression of neuropathy among the AIDS subjects may result from cytokine production by macrophage/monocytes in situ in DRGs.