Gutierrez E G, Banks W A, Kastin A J
Veterans Affairs Medical Center, New Orleans, LA 70146.
J Neuroimmunol. 1994 Dec;55(2):153-60. doi: 10.1016/0165-5728(94)90005-1.
Recent work has shown that interleukin-1 alpha (IL-1 alpha) and IL-1 beta are transported from blood to brain across the blood-brain barrier by a saturable system. Here, we show that the endogenous IL-1 receptor antagonist (IL-1ra) radioactively labeled with either 125I or 35S is also transported across the blood-brain barrier by a saturable transport system. Between 0.33 and 0.65% of an intravenous dose of labeled IL-1ra entered each gram of brain. The three cytokines inhibited each other's transport in a way suggesting that their elevated blood levels would tend to favor the entry of IL-1 beta at the expense of IL-1 alpha. High performance liquid chromatography confirmed that radioactivity entering the brain represented intact cytokine. Recovery of radioactivity from cerebrospinal fluid, an area without blood vessels, and from the parenchymal fraction of the cortex, and area without circumventricular organs, after capillary depletion confirmed that blood-borne IL-1ra gained entry into the brain. The transport system for IL-1ra appeared to be linked to that for IL-1 alpha and IL-1 beta, but was not affected by IL-2, IL-6, TNF alpha, or MIP-1 alpha. The results show that IL-1ra circulating in the blood can cross the blood-brain barrier to enter the central nervous system.
最近的研究表明，白细胞介素-1α（IL-1α）和白细胞介素-1β（IL-1β）可通过一个可饱和系统从血液穿过血脑屏障运输至脑内。在此，我们发现，用125I或35S放射性标记的内源性白细胞介素-1受体拮抗剂（IL-1ra）同样可通过一个可饱和转运系统穿过血脑屏障。静脉注射剂量的标记IL-1ra中有0.33%至0.65%进入每克脑组织。这三种细胞因子相互抑制对方的运输，这表明它们血液水平的升高往往会有利于IL-1β的进入，而以IL-1α为代价。高效液相色谱法证实进入脑内的放射性代表完整的细胞因子。在毛细血管耗竭后，从无血管区域的脑脊液以及无室周器官区域的皮质实质部分回收放射性，证实血源性IL-1ra进入了脑内。IL-1ra的转运系统似乎与IL-1α和IL-1β的转运系统相关，但不受IL-2、IL-6、肿瘤坏死因子α或巨噬细胞炎性蛋白-1α的影响。结果表明，血液中循环的IL-1ra可穿过血脑屏障进入中枢神经系统。
