McGeer Patrick L, McGeer Edith G
Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
J Neurovirol. 2002 Dec;8(6):529-38. doi: 10.1080/13550280290100969.
Postmortem immunohistochemical studies have revealed a state of chronic inflammation limited to lesioned areas of brain in Alzheimer's disease. Some key actors in this inflammation are activated microglia (brain macrophages), proteins of the classical complement cascade, the pentraxins, cytokines, and chemokines. The inflammation does not involve the adaptive immune system or peripheral organs, but is rather due to the phylogenetically much older innate immune system, which appears to operate in most tissues of the body. Chronic inflammation can damage host tissue and the brain may be particularly vulnerable because of the postmitotic nature of neurons. Many of the inflammatory mediators have been shown to be locally produced and selectively elevated in affected regions of Alzheimer's brain. Moreover, studies of tissue in such degenerative processes as atherosclerosis and infarcted heart suggest a similar local innate immune reaction may be important in such conditions. Much epidemiological and limited clinical evidence suggests that nonsteroidal anti-inflammatory drugs may impede the onset and slow the progression of Alzheimer's disease. But these drugs strike at the periphery of the inflammatory reaction. Much better results might be obtained if drugs were found that could inhibit the activation of microglia or the complement system in brain, and combinations of drugs aimed at different inflammatory targets might be much more effective than single agents.
尸检免疫组织化学研究显示，在阿尔茨海默病中，慢性炎症状态仅限于脑损伤区域。这种炎症中的一些关键因素包括活化的小胶质细胞（脑巨噬细胞）、经典补体级联反应的蛋白质、五聚蛋白、细胞因子和趋化因子。这种炎症不涉及适应性免疫系统或外周器官，而是源于进化上更为古老的先天免疫系统，该系统似乎在身体的大多数组织中发挥作用。慢性炎症会损害宿主组织，而由于神经元的终末有丝分裂特性，大脑可能特别脆弱。许多炎症介质已被证明在阿尔茨海默病大脑的受影响区域局部产生并选择性升高。此外，对动脉粥样硬化和梗死心脏等退行性病变组织的研究表明，类似的局部先天免疫反应在这些情况下可能很重要。许多流行病学和有限的临床证据表明，非甾体抗炎药可能会阻碍阿尔茨海默病的发病并减缓其进展。但这些药物作用于炎症反应的外周。如果能找到能抑制脑内小胶质细胞或补体系统活化的药物，可能会取得更好的效果，针对不同炎症靶点的联合用药可能比单一药物更有效。
