Araujo D M, Lapchak P A
University of Southern California, Dept. of Neurogerontology, Andrus Gerontology Center, Los Angeles 90089-0191.
Neuroscience. 1994 Aug;61(4):745-54. doi: 10.1016/0306-4522(94)90398-0.
The present study determined whether molecules normally associated with immune signalling processes, specifically the lymphokines interleukin-1 beta, -2, -3 and -6, can be detected in the human hippocampal formation, and whether their levels are altered in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Interleukin-1 beta, -2, -3 and -6 were measured in post mortem tissues from 14 control neurologically normal subjects, 24 patients with Alzheimer's disease and 17 patients with Parkinson's disease. In order to assess the extent of the cholinergic deficit in the Alzheimer's disease brains, choline acetyltransferase activity in the hippocampal formation was first determined. In the Alzheimer's disease tissues, choline acetyltransferase activity was significantly reduced (by 58%) compared to the control hippocampi, whereas that in the Parkinson's disease hippocampi was not significantly different from control. Using radioimmunoassays with antisera specific for the respective interleukin, marked increases in the content of immunoreactive interleukin-1 beta (99%), interleukin-2 (129%) and interleukin-3 (64%) could be detected in the Alzheimer's, but not the Parkinson's disease hippocampi. Interleukin-6 levels were not significantly different in either group, compared to the control hippocampi. Since striking elevations in various interleukins were detected in the Alzheimer's disease hippocampi, the possibility that concomitant alterations in interleukin receptor sites also occurred was investigated. Using radioligand binding to hippocampal membranes, low levels of interleukin binding were measured in the control hippocampi. In the Alzheimer's tissues, significant elevations in [125I]interleukin-1 beta (by 65%) and [125I]interleukin-2 (by 69%) binding were noted. In contrast, [125I]interleukin-3 binding was not different in the Alzheimer's disease compared to the control tissues. In the hippocampal formation of Parkinson's disease brains, only [125I]interleukin-2 binding was significantly increased (by 80%). In summary, the present results indicate that there is pronounced activation of immune system function, particularly specific immune mediators such as the interleukins, in the hippocampal formation in Alzheimer's disease, and further suggest that stimulation of immune function may be an integral component of the pathological changes that occur in this disease.
本研究旨在确定通常与免疫信号传导过程相关的分子，特别是淋巴因子白细胞介素-1β、-2、-3和-6，是否能在人类海马结构中被检测到，以及它们的水平在诸如阿尔茨海默病和帕金森病等神经退行性疾病中是否会发生改变。对14名神经系统正常的对照受试者、24名阿尔茨海默病患者和17名帕金森病患者的死后组织进行了白细胞介素-1β、-2、-3和-6的检测。为了评估阿尔茨海默病大脑中胆碱能缺陷的程度，首先测定了海马结构中的胆碱乙酰转移酶活性。在阿尔茨海默病组织中，与对照海马相比，胆碱乙酰转移酶活性显著降低（降低了58%），而帕金森病海马中的胆碱乙酰转移酶活性与对照无显著差异。使用针对各自白细胞介素的特异性抗血清进行放射免疫测定，在阿尔茨海默病海马中可检测到免疫反应性白细胞介素-1β（增加99%）、白细胞介素-2（增加129%）和白细胞介素-3（增加64%）含量的显著升高，但在帕金森病海马中未检测到。与对照海马相比，两组中白细胞介素-6水平均无显著差异。由于在阿尔茨海默病海马中检测到各种白细胞介素显著升高，因此研究了白细胞介素受体位点是否也同时发生改变的可能性。通过对海马膜进行放射性配体结合实验，在对照海马中检测到低水平的白细胞介素结合。在阿尔茨海默病组织中，观察到[125I]白细胞介素-1β结合（增加65%）和[125I]白细胞介素-2结合（增加69%）显著升高。相比之下，阿尔茨海默病组织中[125I]白细胞介素-3结合与对照组织无差异。在帕金森病大脑的海马结构中，只有[125I]白细胞介素-2结合显著增加（增加80%）。总之，目前的结果表明，在阿尔茨海默病的海马结构中存在免疫系统功能的明显激活，特别是白细胞介素等特异性免疫介质的激活，并且进一步表明免疫功能的刺激可能是该疾病发生的病理变化的一个组成部分。
