Dantzer R, Bluthé R M, Layé S, Bret-Dibat J L, Parnet P, Kelley K W
Neurobiologie Intégrative, INSERM, Bordeaux, France.
Ann N Y Acad Sci. 1998 May 1;840:586-90. doi: 10.1111/j.1749-6632.1998.tb09597.x.
Peripheral and central injections of interleukin-1 (IL-1) and lipopolysaccharide (LPS) induce the expression of proinflammatory cytokines in the brain and have profound depressing effects on spontaneous and learned behaviors. These effects are mediated by vagal afferents, because they are abrogated by section of the vagus nerves at the subdiaphragmatic level in rats and mice. Vagotomy does not interfere with the synthesis and release of proinflammatory cytokines at the periphery, because plasma and tissue levels of interleukin-1 of vagotomized animals are similar to those of sham-operated animals. Furthermore, the consequences of vagotomy on the host behavioral response to peripheral cytokines are specific to the intraperitoneal route of administration of cytokines because vagotomized animals are still able to respond to IL-1 injected intravenously, subcutaneously, and into the lateral ventricle of the brain. Finally, substance P and cholecystokinin do not appear to play a key role in the transmission of the immune message to the brain because pretreatment by capsaicin or by specific antagonists of CCKA and CCKB receptors does not alter the behavioral effects of LPS and IL-1. All these findings point to the role of neural afferents for transmitting the immune message from the periphery to the brain.
外周和中枢注射白细胞介素-1（IL-1）和脂多糖（LPS）可诱导大脑中促炎细胞因子的表达，并对自发行为和习得行为产生显著的抑制作用。这些作用是由迷走神经传入介导的，因为在大鼠和小鼠的膈下水平切断迷走神经后，这些作用就会消失。迷走神经切断术不会干扰外周促炎细胞因子的合成和释放，因为迷走神经切断动物的白细胞介素-1血浆和组织水平与假手术动物相似。此外，迷走神经切断术对宿主对外周细胞因子行为反应的影响仅限于细胞因子的腹腔内给药途径，因为迷走神经切断动物仍能对静脉内、皮下和脑侧脑室内注射的IL-1作出反应。最后，P物质和胆囊收缩素似乎在免疫信息向大脑的传递中不发挥关键作用，因为用辣椒素或CCKA和CCKB受体的特异性拮抗剂预处理不会改变LPS和IL-1的行为效应。所有这些发现都表明神经传入在将免疫信息从外周传递到大脑中所起的作用。
