Molecular basis of sickness behavior
Molecular basis of sickness behavior
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DOI：
10.1111/j.1749-6632.1998.tb08321.x
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Kelley, KW
中科院分区：
文献类型：
--
作者：
Dantzer, R;Bluthé, RM;Kelley, KW
外周和中枢注射脂多糖（LPS）（一种细胞因子诱导剂）和重组促炎细胞因子（如白细胞介素-1 β（IL-1 β））可诱导食物摄入减少和社会活动减少形式的疾病行为。在过去的3年中，细胞因子的行为效应的机制已经成为许多研究的主题。在行为水平上，细胞因子对行为的深刻抑制作用是高度组织化的动机状态的表达。在分子水平上，疾病行为由可诱导的脑细胞因子隔室介导，所述细胞因子隔室由外周细胞因子经由神经传入通路激活。中枢产生的细胞因子作用于脑细胞因子受体，其特征类似于外周免疫和非免疫细胞上的细胞因子受体，如使用细胞因子受体拮抗剂、针对细胞因子受体特定亚型的中和抗体和基因靶向技术的药理学实验所证明。有证据表明，不同的疾病行为的组成部分是由不同的细胞因子介导的，这些细胞因子的相对重要性是不一样的，在外周和中央细胞因子室。
Peripheral and central injections of lipopolysaccharide (LPS), a cytokine inducer, and recombinant proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) induce sickness behavior in the form of reduced food intake and decreased social activities. Mechanisms of the behavioral effects of cytokines have been the subject of much investigation during the last 3 years. At the behavioral level, the profound depressing effects of cytokines on behavior are the expression of a highly organized motivational state. At the molecular level, sickness behavior is mediated by an inducible brain cytokine compartment that is activated by peripheral cytokines via neural afferent pathways. Centrally produced cytokines act on brain cytokine receptors that are similar to those characterized on peripheral immune and nonimmune cells, as demonstrated by pharmacologic experiments using cytokine receptor antagonists, neutralizing antibodies to specific subtypes of cytokine receptors, and gene targeting techniques. Evidence exists that different components of sickness behavior are mediated by different cytokines and that the relative importance of these cytokines is not the same in the peripheral and central cytokine compartments.