Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve.
Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve.
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DOI：
10.1084/jem.20042397
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发表时间：
2005-10-17
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脊椎动物的免疫系统通过复杂的细胞和体液过程感知外源性和内源性危险信号，并通过炎症反应做出反应以对抗假定的攻击。强大的保护性免疫力是防止病原体入侵的必要条件；然而，必须避免对肠道内的共生菌群和膳食成分产生相同的反应。自主神经系统通过硬连线连接和化学信使（例如缩胆囊素（CCK））在感知肠道内的管腔内容物方面发挥着重要作用。在此，我们报告膳食脂肪的摄入会刺激 CCK 受体，并通过传出迷走神经和烟碱受体导致炎症反应减弱。迷走神经切断术和给予CCK和烟碱受体拮抗剂可显着减弱高脂肠内营养对失血性休克诱导的肿瘤坏死因子-α和白细胞介素6释放的抑制作用（P < 0.05）。此外，高脂肠内营养对炎症诱导的肠道通透性的保护作用被迷走神经切断术和 CCK 和烟碱受体拮抗剂的施用所消除。这些数据揭示了一种由营养控制的新型神经免疫途径，可能有助于解释肠道对饮食抗原的低反应性，并为营养的功能提供新的线索。
The immune system in vertebrates senses exogenous and endogenous danger signals by way of complex cellular and humoral processes, and responds with an inflammatory reaction to combat putative attacks. A strong protective immunity is imperative to prevent invasion of pathogens; however, equivalent responses to commensal flora and dietary components in the intestine have to be avoided. The autonomic nervous system plays an important role in sensing luminal contents in the gut by way of hard-wired connections and chemical messengers, such as cholecystokinin (CCK). Here, we report that ingestion of dietary fat stimulates CCK receptors, and leads to attenuation of the inflammatory response by way of the efferent vagus nerve and nicotinic receptors. Vagotomy and administration of antagonists for CCK and nicotinic receptors significantly blunted the inhibitory effect of high-fat enteral nutrition on hemorrhagic shock-induced tumor necrosis factor-α and interleukin-6 release (P < 0.05). Furthermore, the protective effect of high-fat enteral nutrition on inflammation-induced intestinal permeability was abrogated by vagotomy and administration of antagonists for CCK and nicotinic receptors. These data reveal a novel neuroimmunologic pathway, controlled by nutrition, that may help to explain the intestinal hyporesponsiveness to dietary antigens, and shed new light on the functionality of nutrition.