Banks W A, Kastin A J, Gutierrez E G
Veterans Affairs Medical Center, New Orleans, LA 70146.
Neurosci Lett. 1993 Nov 26;163(1):41-4. doi: 10.1016/0304-3940(93)90224-9.
Interleukin-1 alpha (IL-1 alpha), an immunoregulatory protein secreted by the peripheral immune system, affects the central nervous system (CNS). IL-1 alpha could directly enter the parenchyma of the brain in intact form to alter brain function, or it could be blocked or sequestered by the capillary bed comprising the blood-brain barrier (BBB) that normally retards entry of circulating proteins to the brain and cerebrospinal fluid (CSF). We show here by use of the selective interleukin receptor antagonist (IL-1ra), capillary depletion method, high performance liquid chromatography (HPLC) and saturation with unlabeled IL-1 alpha that radioactively labeled IL-1 alpha injected iv directly enters the CNS in intact form. This also occurs in the brain cortex, an area devoid of circumventricular organs (CVOs), and in the CSF, an area devoid of capillaries. Capillaries can also sequester IL-1 alpha in a saturable manner, suggesting that they may be the site for the carrier-mediated entry of IL-1 alpha into the CNS. Thus, the results show that circulating IL-1 alpha has direct access to cortical brain cells behind the BBB through a saturable transport system that provides a major pathway by which the brain and immune system interact.
白细胞介素-1α（IL-1α）是一种由外周免疫系统分泌的免疫调节蛋白，会影响中枢神经系统（CNS）。IL-1α可以完整形式直接进入脑实质以改变脑功能，或者它可能被构成血脑屏障（BBB）的毛细血管床阻断或隔离，血脑屏障通常会阻碍循环蛋白进入脑和脑脊液（CSF）。我们在此通过使用选择性白细胞介素受体拮抗剂（IL-1ra）、毛细血管耗竭法、高效液相色谱（HPLC）以及用未标记的IL-1α饱和的方法表明，静脉注射放射性标记的IL-1α能以完整形式直接进入中枢神经系统。这在没有室周器官（CVO）的脑皮质区域以及没有毛细血管的脑脊液区域也会发生。毛细血管也能以饱和方式隔离IL-1α，这表明它们可能是IL-1α通过载体介导进入中枢神经系统的部位。因此，结果表明循环中的IL-1α可通过一个饱和转运系统直接进入血脑屏障后的皮质脑细胞，该转运系统为脑与免疫系统相互作用提供了一条主要途径。
