Hansen M K, Taishi P, Chen Z, Krueger J M
Department of Physiology and Biophysics, The University of Tennessee, Memphis, Tennessee 38163, USA.
J Neurosci. 1998 Mar 15;18(6):2247-53. doi: 10.1523/JNEUROSCI.18-06-02247.1998.
There is considerable interest in the mechanisms by which systemic cytokines signal the CNS to elicit centrally controlled biological actions. This study determined the effects of intraperitoneal injections of interleukin-1beta (IL-1beta) on IL-1beta mRNA and IL-1 receptor accessory protein (IL-1RAP) mRNA production in rat liver and brain using the reverse transcription-PCR. Saline or IL-1beta (0.5 microg/kg) was injected intraperitoneally in subdiaphragmatically vagotomized and sham-operated (SHAM) rats. All injections were performed at dark onset, and rats were killed 2 hr after the injection. In SHAM rats, IL-1beta increased IL-1beta mRNA levels in the liver, hypothalamus, hippocampus, and brainstem. Subdiaphragmatic vagotomy blocked the IL-1beta-induced increase in IL-1beta mRNA in the brainstem and hippocampus and significantly attenuated the increase in the hypothalamus. Vagotomy did not affect IL-1beta-induced IL-1beta mRNA production in the liver. IL-1RAP mRNA was highly expressed in each region examined; however, no significant differences in IL-1RAP mRNA production were found in any region after IL-1beta injection. The current results indicate that the vagus nerve is involved in transmitting cytokine signals to the brain and suggest that the induction of brain cytokines is a critical step in the pathway by which vagal-mediated signals result in centrally controlled symptoms of the acute phase response.
全身细胞因子向中枢神经系统发出信号以引发中枢控制的生物学作用的机制备受关注。本研究使用逆转录 - 聚合酶链反应确定了腹腔注射白细胞介素 - 1β（IL - 1β）对大鼠肝脏和大脑中IL - 1β信使核糖核酸（mRNA）和IL - 1受体辅助蛋白（IL - 1RAP）mRNA产生的影响。在膈下迷走神经切断和假手术（SHAM）大鼠中腹腔注射生理盐水或IL - 1β（0.5微克/千克）。所有注射均在黑暗开始时进行，注射后2小时处死大鼠。在SHAM大鼠中，IL - 1β增加了肝脏、下丘脑、海马体和脑干中IL - 1β mRNA水平。膈下迷走神经切断术阻断了IL - 1β诱导的脑干和海马体中IL - 1β mRNA的增加，并显著减弱了下丘脑中的增加。迷走神经切断术不影响IL - 1β诱导的肝脏中IL - 1β mRNA的产生。IL - 1RAP mRNA在每个检测区域中均高度表达；然而，注射IL - 1β后，在任何区域中IL - 1RAP mRNA产生均未发现显著差异。当前结果表明迷走神经参与将细胞因子信号传递至大脑，并提示脑内细胞因子的诱导是迷走神经介导的信号导致急性期反应中枢控制症状途径中的关键步骤。
