Garlind A, Brauner A, Höjeberg B, Basun H, Schultzberg M
Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Division of Geriatric Medicine, Huddinge University Hospital, S-141 86, Huddinge, Sweden.
Brain Res. 1999 Apr 24;826(1):112-6. doi: 10.1016/s0006-8993(99)01092-6.
Evidence from epidemiological, clinical and experimental studies favour the hypothesis that inflammatory events are part of the neuropathology in Alzheimer's disease. Proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) have been found in activated microglia in the vicinity of amyloid plaques in Alzheimer's disease brain. In the present study, the levels of soluble IL-1 receptor type II (sIL-1R type II), IL-1 receptor antagonist (IL-1ra), IL-1beta, IL-6 and TNF-alpha were analyzed in cerebrospinal fluid (CSF) samples from Alzheimer's disease patients and control subjects. The levels of sIL-1R type II were significantly higher in CSF from Alzheimer's disease patients than in CSF samples from control subjects (38.5+/-8 pg/ml (mean+/-S.E.M.) vs. 7.9+/-4 pg/ml, p<0.05). Measurements of the proinflammatory cytokines IL-6 and TNF-alpha showed no significant difference between the two groups, and the levels of IL-1beta and IL-1ra in the present material were too low to permit detection. The increased levels of sIL-1R type II may reflect a compensatory mechanism to balance an increased release of IL-1 receptor agonists in the Alzheimer's disease brain.
流行病学、临床及实验研究的证据支持如下假说:炎症反应是阿尔茨海默病神经病理学的一部分。在阿尔茨海默病患者大脑中淀粉样斑块附近的活化小胶质细胞中已发现促炎细胞因子,如白细胞介素-1(IL-1)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)。在本研究中,分析了阿尔茨海默病患者和对照受试者脑脊液(CSF)样本中可溶性II型IL-1受体(sIL-1R II型)、IL-1受体拮抗剂(IL-1ra)、IL-1β、IL-6和TNF-α的水平。阿尔茨海默病患者脑脊液中sIL-1R II型水平显著高于对照受试者脑脊液样本(38.5±8 pg/ml(均值±标准误)对7.9±4 pg/ml,p<0.05)。促炎细胞因子IL-6和TNF-α的检测显示两组之间无显著差异,且本研究材料中IL-1β和IL-1ra的水平过低无法检测。sIL-1R II型水平升高可能反映了一种代偿机制,以平衡阿尔茨海默病大脑中IL-1受体激动剂释放的增加。