Kapcala L P, He J R, Gao Y, Pieper J O, DeTolla L J
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA.
Brain Res. 1996 Jul 29;728(2):247-54. doi: 10.1016/0006-8993(96)00511-2.
Although interleukin (IL)-1 beta activates the hypothalamic-pituitary-adrenal (HPA) axis, the mechanisms by which peripheral IL-1 beta acutely stimulates adrenocorticotropin (ACTH) secretion are not clear. Recently, the vagus has been implicated in mediating peripheral cytokine signalling of the brain. To investigate a possible central mechanism for peripheral cytokine stimulation of the HPA axis, we tested the hypothesis that the vagus mediates IL-1 beta activation of the HPA axis by an intra-abdominal stimulus. We studied the effect of subdiaphragmatic vagotomy on plasma ACTH stimulation in rats by intraperitoneal (i.p.) IL-1 beta. Adult male Sprague-Dawley rats underwent subdiaphragmatic vagotomy or sham surgery 1 week prior to study. Rats were killed 1 and 2 h after i.p. saline (control) and low- (4 micrograms/kg) and high-dose (20 micrograms/kg) IL-1 beta. Vagotomy markedly attenuated plasma ACTH secretion at 2 h after high-dose IL-1 beta stimulation and abolished plasma ACTH secretion at 2 h after low-dose IL-1 beta stimulation. At 1 h after low-dose IL-1 beta, stimulation of plasma ACTH in vagotomized animals was also markedly diminished compared to sham animals. However, vagotomy did not alter stimulation of plasma corticosterone at 1 or 2 h after low-dose IL-1 beta or at 2 h after high-dose IL-1 beta. In addition, vagotomy did not alter stimulation of plasma ACTH or corticosterone secretion by insulin-induced hypoglycemia. We conclude that: (1) the vagus plays an important role in stimulation of ACTH secretion by intra-abdominal (i.p.) IL-1 beta; (2) stimulation of corticosterone secretion by i.p. IL-1 beta is not altered by vagotomy; and (3) the inhibitory effect of vagotomy on activation of the HPA axis appears to be specific for immune stimulation by cytokines.
尽管白细胞介素（IL）-1β可激活下丘脑-垂体-肾上腺（HPA）轴，但外周IL-1β急性刺激促肾上腺皮质激素（ACTH）分泌的机制尚不清楚。最近，迷走神经被认为参与介导大脑的外周细胞因子信号传导。为了研究外周细胞因子刺激HPA轴的可能中枢机制，我们检验了以下假设：迷走神经通过腹腔内刺激介导IL-1β对HPA轴的激活。我们研究了膈下迷走神经切断术对大鼠腹腔内（i.p.）注射IL-1β后血浆ACTH刺激的影响。成年雄性Sprague-Dawley大鼠在研究前1周接受膈下迷走神经切断术或假手术。在腹腔注射生理盐水（对照）、低剂量（4微克/千克）和高剂量（20微克/千克）IL-1β后1小时和2小时处死大鼠。迷走神经切断术显著减弱了高剂量IL-1β刺激后2小时的血浆ACTH分泌，并消除了低剂量IL-1β刺激后2小时的血浆ACTH分泌。在低剂量IL-1β刺激后1小时，与假手术动物相比，迷走神经切断术动物的血浆ACTH刺激也明显减弱。然而，迷走神经切断术并未改变低剂量IL-1β刺激后1小时或2小时以及高剂量IL-1β刺激后2小时的血浆皮质酮刺激。此外，迷走神经切断术并未改变胰岛素诱导的低血糖对血浆ACTH或皮质酮分泌的刺激。我们得出以下结论：（1）迷走神经在腹腔内（i.p.）IL-1β刺激ACTH分泌中起重要作用；（2）腹腔内注射IL-1β刺激皮质酮分泌不受迷走神经切断术影响；（3）迷走神经切断术对HPA轴激活的抑制作用似乎对细胞因子的免疫刺激具有特异性。
