Dantzer Robert, Bluthé Rose-Marie, Gheusi Gilles, Cremona Sandrine, Layé Sophie, Parnet Patricia, Kelley Keith W
Neurobiologie intégrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cédex, France.
Laboratory of Immunophysiology, Department of Animal Sciences, University of Illinois, Urbana, Illinois 61801, USA.
Ann N Y Acad Sci. 1998 Sep 29;856:132-138. doi: 10.1111/j.1749-6632.1998.tb08321.x.
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.
外周和中枢注射细胞因子诱导剂脂多糖（LPS）以及重组促炎细胞因子，如白细胞介素-1β（IL-1β），会引发以食物摄入量减少和社交活动减少为形式的疾病行为。在过去3年中，细胞因子行为效应的机制一直是大量研究的主题。在行为层面，细胞因子对行为的深刻抑制作用是一种高度有组织的动机状态的表现。在分子层面，疾病行为由一个可诱导的脑内细胞因子区室介导，外周细胞因子通过神经传入途径激活该区域。通过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以及基因靶向技术的药理学实验证明，中枢产生的细胞因子作用于与外周免疫和非免疫细胞上所鉴定的受体相似的脑细胞因子受体。有证据表明，疾病行为的不同组成部分由不同的细胞因子介导，并且这些细胞因子在外周和中枢细胞因子区室中的相对重要性并不相同。
