Main C, Blennerhassett P, Collins S M
Intestinal Diseases Research Unit, McMaster University Medical Centre, Hamilton, Ontario, Canada.
Gastroenterology. 1993 Jun;104(6):1648-54. doi: 10.1016/0016-5085(93)90641-o.
A marked suppression of acetylcholine (ACh) release from myenteric nerves in the inflamed intestine of rats infected by Trichinella spiralis has been shown. In this model, there is increased expression of interleukin 1 beta (IL-1 beta) in the myenteric plexus. Therefore, the ability of IL-1 beta to alter ACh release in longitudinal muscle-myenteric plexus (LMMP) preparations from noninfected rats was examined.
LMMP preparations were loaded with [3H]choline before stimulation by KCl or electrical field stimulation. ACh release was recorded by measuring 3H in the superfusate. Experiments were performed in the presence or absence of human recombinant IL-1 beta.
IL-1 beta had no immediate effect on the basal or stimulated release of ACh. A marked suppression of ACh release was observed in tissues that had been preincubated with IL-1 beta for 60 minutes or more. The effect of IL-1 beta was concentration and time dependent with maximum suppression occurring with 10 ng/mL of the cytokine after a 90-minute incubation. The action of human recombinant (hr) IL-1 beta was abolished by boiling the cytokine for 20 minutes and was prevented by preincubating the cytokine with neutralizing antibody. The IL-1 beta effect was also blocked by cycloheximide and was spontaneously reversible after 60 minutes.
It was concluded that IL-1 beta suppresses ACh release via the formation and release of a protein mediator that could be another cytokine, including IL-1. Based on these findings, we consider IL-1 beta a putative mediator of the changes in cholinergic nerve function observed in the inflamed rat intestine.
已表明，感染旋毛虫的大鼠发炎肠道中，肌间神经释放的乙酰胆碱（ACh）受到显著抑制。在该模型中，肌间神经丛中白细胞介素1β（IL-1β）的表达增加。因此，研究了IL-1β对未感染大鼠纵行肌-肌间神经丛（LMMP）制剂中ACh释放的影响。
在通过氯化钾或电场刺激之前，将[3H]胆碱加载到LMMP制剂中。通过测量灌流液中的3H来记录ACh释放。在有或无重组人IL-1β的情况下进行实验。
IL-1β对ACh的基础释放或刺激释放没有即时影响。在预先用IL-1β孵育60分钟或更长时间的组织中，观察到ACh释放受到显著抑制。IL-1β的作用具有浓度和时间依赖性，孵育90分钟后，10 ng/mL的细胞因子产生最大抑制作用。将细胞因子煮沸20分钟可消除重组人（hr）IL-1β的作用，并用中和抗体预先孵育细胞因子可防止这种作用。IL-1β的作用也被环己酰亚胺阻断，60分钟后可自发逆转。
得出的结论是，IL-1β通过形成和释放一种蛋白质介质来抑制ACh释放，该介质可能是另一种细胞因子，包括IL-1。基于这些发现，我们认为IL-1β是在发炎的大鼠肠道中观察到的胆碱能神经功能变化的一种假定介质。
