Histopathological and blood-brain barrier changes in rats induced by an intracerebral injection of human recombinant interleukin 2.
Histopathological and blood-brain barrier changes in rats induced by an intracerebral injection of human recombinant interleukin 2.
复制标题
脑内注射人重组白细胞介素2诱导大鼠的组织病理学和血脑屏障变化。
DOI：
10.1097/00006123-198908000-00008
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发表时间：
1989
期刊：
影响因子：
4.8
通讯作者：
Merchant,RE
中科院分区：
文献类型：
--
作者：
Watts,RG;Wright,JL;Atkinson,LL;Merchant,RE
利用人重组白细胞介素2（rIL-2）联合淋巴因子激活的杀伤细胞的连续性免疫疗法在治疗各种类型的癌症，特别是肾癌和黑色素瘤中显示出一定的疗效。静脉注射rIL-2，有或没有淋巴因子激活的杀伤细胞，产生各种严重的副作用，约三分之一的患者经历神经系统状态的下降。我们以前在动物中的研究表明，单次静脉注射rIL-2可以损害血脑屏障（BBB）的完整性。本研究观察了大鼠顶叶单次脑内注射rIL-2、其赋形剂或生理盐水后的组织病理学效应和血脑屏障变化。在长达8天的不同时间间隔（静脉注射辣根过氧化物酶后1小时）处死动物，将脑组织切片并进行光学显微镜检查。在注射后4、12和24小时，由于创伤性血脑屏障破坏，所有动物均显示辣根过氧化物酶脑血管通透性增加。仅在注射rIL-2的动物中，辣根过氧化物酶外渗持续3天和8天。注射rIL-2导致注射部位白细胞浸润增加、血管周围套囊和24小时局部水肿，在8天研究期间持续增加。这些结果表明，单次注射人rIL-2到大鼠脑中诱导白细胞流入脑中，并可能有助于使创伤诱导的BBB完整性受损永久化的细胞事件。（神经外科25：202-208，1989）
: Adoptive immunotherapy utilizing human recombinant interleukin 2 (rIL-2) in conjunction with lymphokine-activated killer cells has shown some efficacy in the treatment of various types of cancers, particularly renal carcinoma and melanoma. Intravenous administration of rIL-2, with or without lymphokine-activated killer cells, produces a variety of serious side effects and approximately one-third of the patients experience a decrease in neurological status. Our previous investigations in animals have indicated that a single intravenous injection of rIL-2 can compromise the integrity of the blood-brain barrier (BBB). The present study examined the histopathological effect and BBB changes in rats which occur after a single intracerebral injection of rIL-2, its excipient, or saline into the parietal lobe. Animals were killed at various intervals up to 8 days (1 hour after intravenous injection of horseradish peroxidase), and the brain tissue was sectioned and processed for light microscopy. All animals showed increased cerebrovascular permeability for horseradish peroxidase due to traumatic BBB disruption at 4, 12, and 24 hours after injection. Extravasation of horseradish peroxidase persisted at 3 and 8 days only in animals injected with rIL-2. Injections of rIL-2 led to an increased leukocytic infiltration into the injection site, perivascular cuffing, and localized edema by 24 hours, which continued to increase over the 8-day study period. These results suggest that a single injection of human rIL-2 into the brain of rats induces an influx of leukocytes into the brain and may contribute to the cellular events that perpetuate a trauma-induced compromise in the integrity of the BBB.(Neurosurgery 25: 202-208, 1989)