Banks W A, Kastin A J
Veterans Affairs Medical Center, New Orleans, LA 70146.
Int J Immunopharmacol. 1992 May;14(4):629-36. doi: 10.1016/0192-0561(92)90124-4.
Previous studies have suggested that some of the central nervous system (CNS) effects of interleukin-2 (IL-2) and perhaps other cytokines might be mediated through disruption of the blood-brain barrier (BBB). We investigated the ability of human IL-2 and, in selected studies, human IL-1 alpha and human IL-1 beta to disrupt the BBB to radioiodinated bovine serum albumin (RISA) after intravenous (i.v.) and intracerebroventricular (i.c.v.) injection. No disruption of the BBB occurred for up to 2 h after the i.v. injection of 2 micrograms/mouse of IL-2 (10(5) U/kg of body weight), 2 micrograms of IL-1 alpha (10(7) U/kg), or 2 micrograms of IL-1 beta (10(7) U/kg). This dose of i.v. IL-2 also did not affect BBB permeability to RISA in the brain to blood direction. Damage to the BBB induced by hypertension elicited by i.v. epinephrine was not enhanced or prolonged by IL-2. When given directly into the CNS by the i.c.v. route, 100 ng of IL-2 (2.2 x 10(5) U/kg of brain), 100 ng of IL-1 alpha (2.2 x 10(7) U/kg of brain), or 100 ng of IL-1 beta (2.2 x 10(7) U/kg of brain) had no effect on BBB integrity in either the blood to brain or the brain to blood direction. We conclude that the effects of IL-1 alpha, IL-1 beta, and IL-2 on the CNS, as studied under these conditions, are not due to disruption of the BBB but are mediated by other mechanisms including the ability of some interleukins to cross the BBB by a saturable transport system described previously.
先前的研究表明，白细胞介素-2（IL-2）以及或许其他细胞因子对中枢神经系统（CNS）的某些作用可能是通过破坏血脑屏障（BBB）介导的。我们研究了人IL-2以及在选定研究中的人IL-1α和人IL-1β在静脉内（i.v.）和脑室内（i.c.v.）注射后破坏血脑屏障对放射性碘化牛血清白蛋白（RISA）通透性的能力。静脉注射2微克/小鼠的IL-2（10⁵U/千克体重）、2微克的IL-1α（10⁷U/千克）或2微克的IL-1β（10⁷U/千克）后，长达2小时血脑屏障未发生破坏。该剂量的静脉注射IL-2也未影响脑内血脑屏障对RISA从脑到血方向的通透性。静脉注射肾上腺素引起的高血压对血脑屏障造成的损害未因IL-2而增强或延长。当通过脑室内途径直接给予中枢神经系统时，100纳克的IL-2（2.2×10⁵U/千克脑）、100纳克的IL-1α（2.2×10⁷U/千克脑）或100纳克的IL-1β（2.2×10⁷U/千克脑）对血脑屏障在血到脑或脑到血方向的完整性均无影响。我们得出结论，在这些条件下所研究的IL-1α、IL-1β和IL-2对中枢神经系统的作用并非由于血脑屏障的破坏，而是由其他机制介导的，包括一些白细胞介素通过先前描述的可饱和转运系统穿过血脑屏障的能力。
