A study on the cytokine regulation of the hypothalamo-pituitary-adrenal system in the rat

越来越多的证据表明，在细菌感染过程中激活的免疫细胞产生的各种细胞因子能够刺激人和动物的下丘脑-垂体-肾上腺（HPA）轴。然而，在这一研究领域仍有大量尚未解决的问题。在这项研究中，我们在大鼠中进行了一些实验，以更好地了解该物种中HPA轴的细胞因子调节。本研究中进行的具体实验和从每个实验中获得的影响总结如下。（1）利用脑推拉灌流（PPP）技术，研究了白细胞介素（IL）-1 β在促肾上腺皮质激素释放激素（CRH）神经元系统中的作用部位。我们获得的数据表明，IL-1 β可能作用于室旁核（PVN，CRH神经元细胞体的定位部位）和正中隆起（ME，CRH神经元轴突纤维终止的部位）。 ...更多信息 此外，研究还表明，不仅CRH，而且精氨酸加压素（AVP）也可能介导IL-1 β刺激ACTH分泌。（2）再次利用PPP方法，研究了前列腺素（PG）E_2在IL-1 β刺激ACTH分泌中的作用。静脉注射IL-1 β后，下丘脑室旁核PGE_2含量显著升高，而下丘脑视前区和视神经节区PGE_2含量无明显变化，且下丘脑室旁核PGE_2含量的升高与下丘脑同一区CRH和AVP含量的升高同步。本实验利用脑内神经肽免疫中和技术，研究了垂体促肾上腺皮质激素（ACTH）分泌素如催产素（OT）、血管紧张素Ⅱ（A Ⅱ）和胆囊收缩素（CCK）-8等是否与垂体促肾上腺皮质激素（ACTH）的分泌有关。也参与脑室内（icv）给予IL-1 β诱导的ACTH反应。通过icv注射抗这些肽的抗血清，我们得到的数据表明，A Ⅱ，而不是OT或CCK-8，可能介导IL-1 β刺激ACTH分泌。此外，利用相同的技术，我们研究了CRH和AVP是否有助于通过icv注射IL-6和肿瘤坏死因子（TNF）-α诱导的ACTH反应。提示IL-6诱导的ACTH反应可能由CRH和AVP共同介导，而ACTH对TNF-α的反应仅通过CRH介导。少

A growing body of evidence suggests that various cytokines produced by activated immune cells during bacterial infection are able to stimulate the hypothalamo-pituitary-adrenal (HPA) axis in humams and animals. However, there are a great number of as yet unanswered problems in this area of research. In this study, we conducted a couple of experiments in rats to have a better understanding of the cytokine regulation of the HPA axis in this species. Specific experiments performed in the present study and implications obtained from each of them are summarized below.(1)Utilizing the technique of push-pull perfusion (PPP) of the brain, we examined the site of action of interleukin (IL) -1beta within the corticotropinreleasing hormone (CRH) neuronal system. We obtained the data suggesting that IL-1beta may act on both the paraventricular nucleus (PVN,the site where CRH neuronal cell bodies are localized) and the median eminence (ME,the site where axonal fibers of CRH neurons are terminated). … More It was also suggested that not only CRH but arginine vasopressin (AVP) may mediate the IL-1beta stimulation of ACTH secretion.(2)Utilizing the PPP method again, we examined the alleged significant role of prostaglandin (PG) E_2 in the IL-1beta stimulation of ACTH secretion. After an intravenous administration of IL-1beta, a significant rise in PGE_2 was observed in the PVN but not in the ME or the preoptic area of the hypothalamus.The increase in PGE_2 in the PVN was in synchrony with the rise in CRH and AVP levels in the same hypothalamic area. These results strongly suggest that PGE_2 in the PVN may be a trigger for the activation of CRH neurons, which then leads to ACTH secretion.Utilizing the technique of immunoneutralization of brain neuropeptides, we examined if other ACTH secretagogues such as oxytocin (OT), angiotensin II(A II), and cholecystokinin (CCK)-8, are also involved in the ACTH response induced by intracerebroventricular (icv) administration of IL-1beta. Through examining the effects of icv injection of antisera against these peptides, we obtained the data suggesting that A II,but not OT or CCK-8, may mediate the IL-1beta stimulation of ACTH secretion. In addition, utilizing the same technique, we examined whether CRH and AVP contribute to the ACTH response induced by icv injection of IL-6 and tumor necrosis factor (TNF)-alpha. It was suggested that IL-6-induced ACTH response may be mediated by both CRH and AVP, whereas the ACTH response to TNF-alpha only via CRH. Less