Martiney J A, Litwak M, Berman J W, Arezzo J C, Brosnan C F
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461.
Am J Pathol. 1990 Dec;137(6):1411-23.
Interleukin-1 is a potent immunomodulator and has been shown to initiate many aspects of the inflammatory response. To determine the effects of IL-1b in the central nervous system (CNS), the rabbit retina was used, adjacent to which factors can be injected with minimal trauma and both pathologic and physiologic effects can be monitored. Intravitreal injection of 300 units of IL-1b induced an alteration in the visual evoked potentials (VEP) that was associated with marked intravascular red blood cell accumulations, hemorrhage, and cellular inflammation of the epiretinal vessels. Analysis of these events showed slowing and occasional hyper-excitability of the compound action potential of the optic tract and of the cortical VEP that correlate with the maximum inflammatory response. Histologic studies show the following: no apparent response occurs within the first 1.5 hours after intraocular challenge; and between 3 and 6 hours after injection an extensive intravascular red blood cell accumulation and progressive hemorrhage is accompanied by an increase in the number of mononuclear (MN) cells and the appearance of polymorphonuclear (PMN) cells. Polymorphonuclear cells continue to increase with time to give a single wave of inflammation that peaks 24 hours after injection, while the number of MN cells steadily increases. These events are associated with changes in the permeability of the blood-brain barrier and correlate with the electrophysiologic dysfunctions. Forty-one hours after injection, MN inflammation, reactive gliosis, and residual PMN inflammation are evident. Neutralization with specific antibody inhibited the responses through 6 hours after injection. It is concluded that the rabbit retina provides a valuable model for the in vivo analysis of CNS inflammation.
白细胞介素-1是一种强效免疫调节剂,已被证明可引发炎症反应的多个方面。为了确定白细胞介素-1β在中枢神经系统(CNS)中的作用,使用了兔视网膜,在其附近注射因子时创伤最小,并且可以监测病理和生理效应。玻璃体内注射300单位白细胞介素-1β可引起视觉诱发电位(VEP)改变,这与视网膜前血管内明显的红细胞积聚、出血和细胞炎症有关。对这些事件的分析表明,视束复合动作电位和皮质VEP出现减慢和偶尔的过度兴奋,这与最大炎症反应相关。组织学研究显示:眼内刺激后最初1.5小时内无明显反应;注射后3至6小时,广泛的血管内红细胞积聚和进行性出血伴有单核细胞(MN)数量增加和多形核细胞(PMN)出现。多形核细胞数量随时间持续增加,在注射后24小时出现单一炎症波峰,而MN细胞数量稳步增加。这些事件与血脑屏障通透性的变化有关,并与电生理功能障碍相关。注射后41小时,MN炎症、反应性胶质增生和残留的PMN炎症明显。用特异性抗体中和可抑制注射后6小时内的反应。结论是兔视网膜为中枢神经系统炎症的体内分析提供了一个有价值的模型。