University Clinic of Hepato-Gastroenterology, University Hospital, Grenoble, France.
University Grenoble Alpes, Grenoble Institute of Neurosciences (GIN), Inserm (U1216), Grenoble, France.
J Intern Med. 2017 Jul;282(1):46-63. doi: 10.1111/joim.12611. Epub 2017 Apr 18.
Inflammatory bowel disease (IBD), that is Crohn's disease (CD) and ulcerative colitis, affects about 1.5 million persons in the USA and 2.2 million in Europe. The pathophysiology of IBD involves immunological, genetic and environmental factors. The treatment is medico-surgical but suspensive. Anti-TNFα agents have revolutionized the treatment of IBD but have side effects. In addition, a non-negligible percentage of patients with IBD stop or take episodically their treatment. Consequently, a nondrug therapy targeting TNFα through a physiological pathway, devoid of major side effects and with a good cost-effectiveness ratio, would be of interest. The vagus nerve has dual anti-inflammatory properties through its afferent (i.e. hypothalamic-pituitary-adrenal axis) and efferent (i.e. the anti-TNFα effect of the cholinergic anti-inflammatory pathway) fibres. We have shown that there is an inverse relationship between vagal tone and plasma TNFα level in patients with CD, and have reported, for the first time, that chronic vagus nerve stimulation has anti-inflammatory properties in a rat model of colitis and in a pilot study performed in seven patients with moderate CD. Two of these patients failed to improve after 3 months of vagus nerve stimulation but five were in deep remission (clinical, biological and endoscopic) at 6 months of follow-up and vagal tone was restored. No major side effects were observed. Thus, vagus nerve stimulation provides a new therapeutic option in the treatment of CD.
炎症性肠病(IBD),即克罗恩病(CD)和溃疡性结肠炎,影响美国约 150 万人和欧洲约 220 万人。IBD 的病理生理学涉及免疫、遗传和环境因素。治疗是医学和手术治疗,但有暂停治疗的情况。抗 TNFα 药物已经彻底改变了 IBD 的治疗方法,但有副作用。此外,相当一部分 IBD 患者停止或间歇性地接受治疗。因此,通过生理途径靶向 TNFα 的非药物治疗方法,没有重大副作用且具有良好的成本效益比,将是非常有意义的。迷走神经通过其传入纤维(即下丘脑-垂体-肾上腺轴)和传出纤维(即胆碱能抗炎途径的抗 TNFα 作用)具有双重抗炎特性。我们已经表明,CD 患者的迷走神经张力与血浆 TNFα 水平呈负相关,并且首次报道慢性迷走神经刺激在结肠炎大鼠模型和七例中度 CD 患者的初步研究中具有抗炎作用。这两名患者在迷走神经刺激 3 个月后没有改善,但 5 名患者在 6 个月的随访中处于深度缓解(临床、生物学和内镜),并且迷走神经张力得到恢复。未观察到重大副作用。因此,迷走神经刺激为 CD 的治疗提供了一种新的治疗选择。