Named Series: Twenty Years of Brain, Behavior, and Immunity Twenty years of research on cytokine-induced sickness behavior
Named Series: Twenty Years of Brain, Behavior, and Immunity Twenty years of research on cytokine-induced sickness behavior
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发表时间：
2007
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通讯作者：
R. Dantzer;K. Kelley
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作者：
R. Dantzer;K. Kelley
在干扰素、IL-1和IL-2的克隆和表达的几年内，细胞因子诱导的疾病行为被认识到，这发生在1987年第一期《脑、行为和免疫》出版的时候。I期临床试验证实，向癌症患者注射重组细胞因子会导致各种心理障碍。随后显示，感染后出现的促炎细胞因子的生理浓度在脑中起作用以诱导常见的疾病症状，例如食欲不振、嗜睡、退出正常的社会活动、发烧、关节疼痛和疲劳。这种综合征被认为是病态行为，现在被认为是动机系统的一部分，该系统重新组织生物体的优先级，以促进从感染中恢复。细胞因子向大脑传达外周发生感染的信息，细胞因子的这种作用可以通过血液的传统内分泌途径或通过迷走神经的直接神经传递发生。所有哺乳动物和鸟类都有患病行为，这表明免疫系统和大脑之间的通讯在进化上是保守的，并形成了一种重要的生理适应性反应，有利于生物体在感染期间的生存。细胞因子在脑中起作用以诱导促进存活的生理适应的事实已经导致了这样的假设，即先天免疫系统的不适当的、延长的激活可能涉及脑中的许多病理性紊乱，从阿尔茨海默病到中风。相反，新近发现的细胞因子在从慢性心力衰竭到肥胖的各种系统性共病中的作用，可能开始解释这些受试者精神状态的变化。事实上，大脑中细胞因子作用的最新发现为某些精神疾病（包括抑郁症）的病理生理学提供了一些最重要的线索。时机已经成熟，开始将这些在小鼠身上的基本发现转移到人类身上，并且一些药理学工具已经可以用来拮抗细胞因子的有害作用。出版社：Elseiver Inc.
Cytokine-induced sickness behavior was recognized within a few years of the cloning and expression of interferon-, IL-1 and IL-2, which occurred around the time that the Wrst issue of Brain, Behavior, and Immunity was published in 1987. Phase I clinical trials established that injection of recombinant cytokines into cancer patients led to a variety of psychological disturbances. It was subsequently shown that physiological concentrations of proinXammatory cytokines that occur after infection act in the brain to induce common symptoms of sickness, such as loss of appetite, sleepiness, withdrawal from normal social activities, fever, aching joints and fatigue. This syndrome was deWned as sickness behavior and is now recognized to be part of a motivational system that reorganizes the organism’s priorities to facilitate recovery from the infection. Cytokines convey to the brain that an infection has occurred in the periphery, and this action of cytokines can occur via the traditional endocrine route via the blood or by direct neural transmission via the aVerent vagus nerve. The Wnding that sickness behavior occurs in all mammals and birds indicates that communication between the immune system and brain has been evolutionarily conserved and forms an important physiological adaptive response that favors survival of the organism during infections. The fact that cytokines act in the brain to induce physiological adaptations that promote survival has led to the hypothesis that inappropriate, prolonged activation of the innate immune system may be involved in a number of pathological disturbances in the brain, ranging from Alzheimer’s disease to stroke. Conversely, the newly-deWned role of cytokines in a wide variety of systemic comorbid conditions, ranging from chronic heart failure to obesity, may begin to explain changes in the mental state of these subjects. Indeed, the newest Wndings of cytokine actions in the brain oVer some of the Wrst clues about the pathophysiology of certain mental health disorders, including depression. The time is ripe to begin to move these fundamental discoveries in mice to man and some of the pharmacological tools are already available to antagonize the detrimental actions of cytokines. Published by Elseiver Inc.