Spulber S, Bartfai T, Schultzberg M
Karolinska Institutet, Dept. of Neurobiology, Care Sciences and Society, Stockholm, Sweden.
Brain Behav Immun. 2009 Jul;23(5):573-9. doi: 10.1016/j.bbi.2009.02.015. Epub 2009 Mar 1.
The interleukin-1 (IL-1) family is unique in its including an endogenous antagonist of the IL-1 receptor (IL-1ra). IL-1ra has been shown to antagonise IL-1 signalling so effectively, that it came into clinical use within a few years from its discovery. Although barely detectable in the normal brain, IL-1 is dramatically upregulated during neuroinflammation, and also displays peaks of expression in the brain during development, as well as following the induction of long-term potentiation. IL-1 has been ascribed a central role in neuroinflammation accompanying ageing and age-related neurodegenerative conditions. Several experimental models based on genetically modified mice have been used in order to address the role of IL-1 in neurodegeneration and neuroprotection. Most of the findings here are based on the experiments involving a transgenic mouse strain with brain-directed overexpression of human IL-1ra, in which the balance between IL-1 and IL-1ra is permanently tipped towards inhibiting IL-1 signalling. The developmental effects of IL-1 are evident in the altered brain morphology in adult transgenic mice. In addition, IL-1 appears to be central in regulating the elasticity of the brain response to injury. Thus, a number of lines of evidence support the essential role played by IL-1 in development, plasticity, and physiological brain function.
白细胞介素-1（IL-1）家族很独特，因为它包含白细胞介素-1受体（IL-1ra）的内源性拮抗剂。IL-1ra已被证明能非常有效地拮抗IL-1信号传导，以至于在发现后的几年内就进入了临床应用。IL-1在正常大脑中几乎检测不到，但在神经炎症期间会显著上调，在发育过程中以及在诱导长时程增强后，大脑中也会出现表达峰值。IL-1在伴随衰老和与年龄相关的神经退行性疾病的神经炎症中被认为起着核心作用。为了研究IL-1在神经退行性变和神经保护中的作用，已经使用了几种基于基因改造小鼠的实验模型。这里的大多数发现基于涉及人IL-1ra脑定向过表达的转基因小鼠品系的实验，在该品系中，IL-1和IL-1ra之间的平衡永久性地倾向于抑制IL-1信号传导。IL-1的发育影响在成年转基因小鼠改变的脑形态中很明显。此外，IL-1似乎在调节大脑对损伤反应的弹性方面起着核心作用。因此，许多证据支持IL-1在发育、可塑性和生理性脑功能中所起的重要作用。
