QUANTITATION OF HUMAN-IMMUNODEFICIENCY-VIRUS, IMMUNE ACTIVATION FACTORS, AND QUINOLINIC ACID IN AIDS BRAINS
QUANTITATION OF HUMAN-IMMUNODEFICIENCY-VIRUS, IMMUNE ACTIVATION FACTORS, AND QUINOLINIC ACID IN AIDS BRAINS
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DOI：
10.1172/jci116518
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发表时间：
1993-06-01
影响因子：
15.9
通讯作者：
WILEY, CA
中科院分区：
文献类型：
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作者：
ACHIM, CL;HEYES, MP;WILEY, CA
HIV脑炎是不寻常的，因为神经系统损伤发生在神经元或神经胶质细胞没有明显感染的情况下。由于脑中主要的感染细胞是巨噬细胞，因此已经提出从巨噬细胞释放病毒或免疫活化因子可能介导神经损伤。许多研究已经检测了脑脊液（CSF）中免疫活化因子的浓度，然而，这些CSF测量值与HIV脑炎的严重性之间没有相关性（Wiley，C.一、C. L.阿希姆河D. Schrier，M. P. Heyes，J. A. McCutchen和1。格兰特. 1992. AIDS（Phila.）. 6：1299-1307。由于CSF测量可能不代表这些因子的组织浓度，我们检查了10例AIDS尸检脑内HIV p24、喹啉酸（QUIN）、IL-1、IL-3、IL-6、TNF-α和GMCSF的浓度。皮质灰质、皮质白色和深部灰质的均质化和提取显示HIV gp 41免疫染色量与提取的HIV gag蛋白p24之间具有良好的相关性。组织提取物中细胞因子的浓度较低，与HIV脑炎的严重程度无关。轻度HIV脑炎病例的脑提取物显示深部灰质中TNF-α水平升高，而在更严重的病例中，皮质白色和皮质灰质中也发现TNF-α水平升高。与对照值相比，脑组织和CSF QUIN浓度显著增加。QUIN浓度与HIV脑炎的严重程度无关。我们的结论是，组织中TNF-α和QUIN水平的增加可能在HIV相关神经功能障碍的病因学中发挥作用。
HIV encephalitis is unusual in that neurologic damage occurs in the absence of significant infection of neuronal or glial cells. Because the predominant infected cell in the brain is the macrophage, it has been proposed that release of viral or immune activation factors from macrophages may mediate neurologic damage. Numerous studies have examined the concentration of immune activation factors in the cerebrospinal fluid (CSF), however, there has been no correlation between these CSF measurements and severity of HIV encephalitis (Wiley, C. A., C. L. Achim, R. D. Schrier, M. P. Heyes, J. A. McCutchen, and 1. Grant. 1992. AIDS (Phila.). 6:1299-1307. Because CSF measurements may not represent tissue concentrations of these factors, we examined the concentrations of HIV p24, quinolinic acid (QUIN), IL-1, IL-3, IL-6, TNF-alpha, and GMCSF within the brains of 10 AIDS autopsies. Homogenization and extraction of cortical gray, cortical white and deep gray matter showed a good correlation between the amount of HIV gp41 immunostaining and extracted HIV gag protein p24. The concentrations of cytokines were low in the tissue extracts and showed no correlation with severity of HIV encephalitis. Brain extracts from mild cases of HIV encephalitis showed elevated levels of TNF-alpha in deep gray matter, while in more severe cases, elevated TNF-alpha levels were also found within cortical white and cortical gray matter. Brain tissue and CSF QUIN concentrations were substantially increased compared to control values. QUIN concentrations were not correlated with the severity of HIV encephalitis. We conclude that increased tissue levels of TNF-alpha and QUIN may have a role in the etiology of HIV-related neurologic dysfunction.