Yoshioka M, Bradley W G, Shapshak P, Nagano I, Stewart R V, Xin K Q, Srivastava A K, Nakamura S
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Adv Neuroimmunol. 1995;5(3):335-58. doi: 10.1016/0960-5428(95)00012-q.
Central nervous system (CNS) involvement is common during human immunodeficiency virus type-1 (HIV-1) infection. The neurologic disease of the CNS most frequently observed during acquired immunodeficiency syndrome (AIDS) is HIV-1-associated cognitive/motor complex or AIDS dementia complex (ADC), which is most likely a direct consequence of HIV-1 infection of the CNS. The peripheral nervous system (PNS) is also affected in HIV-1-infected individuals and there are several features of immune- and cytokine-related pathogenesis in both the CNS and PNS that are reviewed. Several lines of evidence demonstrate aspects of immune activation in the CNS and peripheral nervous system (PNS) of HIV-1-infected individuals. The relative paucity of HIV-1 expression in contrast to widespread functional and pathologic changes in the CNS and PNS of AIDS patients, and the lack of evidence of productive infection of HIV-1 in neuronal cells in vivo lead to the possibility of indirect or immunopathogenic mechanisms for HIV-1-related neurologic diseases. Proposed mechanisms of neuronal and glial cell damage are injury of oligodendrocytes by tumor necrosis factor-alpha (TNF-alpha) released from activated macrophage/microglia, calcium-dependent excitoneurotoxicity induced by gp120 HIV-1 envelope protein, N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity by quinolinic acid (a product of activated macrophages), cell injury by HIV-1-specific cytotoxic T cells, and apoptosis of oligodendrocytes or neurons triggered by interaction between cell surface receptors and HIV-1 gp120 protein. Common to those mechanisms is the dependence on cellular activation with expression of proinflammatory cytokines (TNF-alpha, interleukin-1). Amplification of activation signals through the cytokine network by macrophage/astrocyte/endothelial cell interactions, and cell-to-cell contact between activated macrophages and neural cells by upregulation of adhesion molecules dramatically enhances the toxic effect of macrophage products. Expression of immunosuppressive cytokines such as interleukin-4, interleukin-6, and transforming growth factor-beta is also increased in the CNS and PNS of HIV-1-infected patients. This may serve as neuroprotective and regenerative mechanism against insults to nervous system tissue.
中枢神经系统（CNS）受累在人类免疫缺陷病毒1型（HIV-1）感染过程中很常见。在获得性免疫缺陷综合征（AIDS）期间最常观察到的中枢神经系统神经疾病是HIV-1相关认知/运动复合体或艾滋病痴呆综合征（ADC），这很可能是HIV-1感染中枢神经系统的直接后果。外周神经系统（PNS）在HIV-1感染个体中也会受到影响，本文将对中枢神经系统和外周神经系统中免疫和细胞因子相关发病机制的几个特征进行综述。有几条证据表明了HIV-1感染个体的中枢神经系统和外周神经系统（PNS）中免疫激活的情况。与艾滋病患者中枢神经系统和外周神经系统广泛的功能和病理变化相比，HIV-1表达相对较少，并且缺乏体内神经元细胞中HIV-1有效感染的证据，这导致了HIV-1相关神经疾病存在间接或免疫致病机制的可能性。提出的神经元和神经胶质细胞损伤机制包括：活化的巨噬细胞/小胶质细胞释放的肿瘤坏死因子-α（TNF-α）对少突胶质细胞的损伤、HIV-1包膜蛋白gp120诱导的钙依赖性兴奋性神经毒性、喹啉酸（活化巨噬细胞的产物）介导的N-甲基-D-天冬氨酸（NMDA）受体介导的神经毒性、HIV-1特异性细胞毒性T细胞对细胞的损伤，以及细胞表面受体与HIV-1 gp120蛋白相互作用触发的少突胶质细胞或神经元凋亡。这些机制的共同之处在于依赖细胞活化以及促炎细胞因子（TNF-α、白细胞介素-1）的表达。巨噬细胞/星形胶质细胞/内皮细胞相互作用通过细胞因子网络放大激活信号，以及活化的巨噬细胞与神经细胞之间通过上调黏附分子进行细胞间接触，极大地增强了巨噬细胞产物的毒性作用。在HIV-1感染患者的中枢神经系统和外周神经系统中，免疫抑制细胞因子如白细胞介素-4、白细胞介素-6和转化生长因子-β的表达也会增加。这可能作为一种针对神经系统组织损伤的神经保护和再生机制。
