IRCCS Fondazione Santa Lucia, Department of Clinical and Behavioral Neurology, Experimental Neuro-psychobiology Lab Via Ardeatina, 306, I-00179 Roma, Italy.
Curr Pharm Des. 2010;16(38):4213-24. doi: 10.2174/138161210794519147.
A large body of evidence on brain development and ageing has revealed that inflammatory processes profoundly affect brain functions during life span of mammalians, including humans. Activation of innate immune mechanisms leading to pro-inflammatory cytokine up-regulation is involved in devastating and disabling human brain illnesses, as Alzheimer's disease (AD), a progressive neurodegenerative disease that causes dementia in the elderly. Emerging data indicates that the cytokine Interleukin (IL)-18, one of the key mediator of inflammation and immune response, has relevance in the physiopathological processes of the brain, by ultimately influencing the integrity of neurons and putatively contributing to AD. In this review, the relationship between specific IL-18-mediated processes and AD neurodegeneration is summarized and clinical studies pointing to a role of the cytokine in the pathology are discussed. Altogether, the presented data indicate that a more complete knowledge of the molecular mechanisms underlying IL-18 implication in neuroinflammatory and neurodegenerative pathways could contribute toward the development of new therapeutic strategies for AD.
大量关于大脑发育和衰老的证据表明，炎症过程在哺乳动物（包括人类）的整个生命周期中都会深刻影响大脑功能。先天免疫机制的激活导致促炎细胞因子的上调，与阿尔茨海默病（AD）等破坏性和使人丧失能力的人类脑部疾病有关，AD 是一种进行性神经退行性疾病，会导致老年人痴呆。新出现的数据表明，细胞因子白细胞介素（IL）-18 是炎症和免疫反应的主要介质之一，与大脑的生理病理过程有关，最终影响神经元的完整性，并可能导致 AD。在这篇综述中，总结了特定的 IL-18 介导的过程与 AD 神经退行性变之间的关系，并讨论了指向细胞因子在病理学中作用的临床研究。总的来说，所呈现的数据表明，更全面地了解 IL-18 参与神经炎症和神经退行性途径的分子机制，可能有助于开发针对 AD 的新治疗策略。
