PATHOGENESIS AND CYTOKINES IN HIV SENSORY NEUROPATHY

HIV 感觉神经病的发病机制和细胞因子

• 批准号: 2269406
• 负责人: WALTER GEORGE BRADLEY
• 金额: $ 40.69万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-02-01 至 1997-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2269406
• 关键词: AIDS; Alphaherpesvirinae; biopsy; cell death; cytokine; cytomegalovirus; human immunodeficiency virus 1; human subject; human tissue; immunocytochemistry; in situ hybridization; inflammation; interleukin 1; interleukin 6; macrophage; monocyte; nervous system disorder; nervous system infection; pathologic process; polymerase chain reaction; tumor necrosis factor alpha; varicella zoster virus; virus replication

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.

中央和周围神经系统和免疫系统是 人类免疫缺陷病毒1型（HIV-1）感染的主要靶标 在患有免疫缺陷综合征（AIDS）的个体中。 这 周围神经病的发病机理尚未阐明。 这 外围感觉系统的结构特征提供 确定神经元损伤的确切机制的可能性 由HIV-1产生，解剖 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。 我们将测试远端进行性感觉的假设 艾滋病的神经病是1）垂死的背部疾病和2） 巨噬细胞分泌的因素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 从 AIDS患者确认HIV-1感染细胞的身份，并确认 机会病毒的存在。 细胞因子的产生将是 与HIV-1的炎症，神经元丧失和复制相关。 活检的疗法神经和死亡的患者死于艾滋病的病后组织 急性死亡控制措施将包括伴随胫骨，胫骨和坐骨神经痛 神经，相应的L5和SL背根神经节，以及整个 脊髓。 将进行形态计量分析以决定是否 是一种真正的死亡神经病，还是由于 多个周围神经病变。 该提议大写了 因艾滋病而死的受试者中神经病的发病率，将导致 确定神经病的发生率和进展是否 艾滋病受试者可能是由细胞因子产生的 DRG中的巨噬细胞/单核细胞原位。