Dopamine mediates vagal modulation of the immune system by electroacupuncture.
Dopamine mediates vagal modulation of the immune system by electroacupuncture.
复制标题
作者：
败血症是医院死亡的主要原因，以前针对败血症的抗炎策略在临床试验中疗效有限，部分原因是它们针对单一细胞因子，实验模型未能模拟临床环境。神经元网络代表了进化选择的生理机制，以控制炎症，可用于治疗炎症和感染性疾病。在这里，我们报告说，坐骨神经激活与电针控制全身炎症和拯救小鼠从多微生物腹膜炎。电针坐骨神经通过诱导多巴脱羧酶的迷走激活，导致肾上腺髓质中多巴胺的产生，从而控制全身炎症。肾上腺切除动物的实验模型模拟临床肾上腺功能不全，增加对败血症的易感性，并阻止电针的抗炎潜力。多巴胺通过多巴胺能1型受体抑制细胞因子的产生。多巴胺能D1受体激动剂抑制全身炎症，并从肾上腺功能不全动物的多微生物腹膜炎中拯救小鼠。我们的研究结果表明，坐骨神经和迷走神经介导的一种新型抗炎机制调节肾上腺中儿茶酚胺的产生。从药理学的角度来看，选择性多巴胺能激动剂模拟电针的抗炎潜力，可以提供治疗优势，以控制感染性和炎症性疾病的炎症。
Previous anti-inflammatory strategies against sepsis, a leading cause of death in hospitals, had limited efficacy in clinical trials, in part because they targeted single cytokines and the experimental models failed to mimic clinical settings. Neuronal networks represent physiological mechanisms selected by evolution to control inflammation that can be exploited for the treatment of inflammatory and infectious disorders. Here, we report that sciatic nerve activation with electroacupuncture controls systemic inflammation and rescues mice from polymicrobial peritonitis. Electroacupuncture at the sciatic nerve controls systemic inflammation by inducing a vagal activation of DOPA decarboxylase leading to the production of dopamine in the adrenal medulla. Experimental models with adrenolectomized animals mimic clinical adrenal insufficiency, increase the susceptibility to sepsis, and prevent the anti-inflammatory potential of electroacupuncture. Dopamine inhibits cytokine production via dopaminergic type-1 receptors. Dopaminergic D1-agonists suppress systemic inflammation and rescue mice from polymicrobial peritonitis in animals with adrenal insufficiency. Our results suggest a novel anti-inflammatory mechanism mediated by the sciatic and the vagus nerves modulating the production of catecholamines in the adrenal glands. From a pharmacological perspective, selective dopaminergic agonists mimic the anti-inflammatory potential of electroacupuncture and can provide therapeutic advantages to control inflammation in infectious and inflammatory disorders.
登录
查看更多内容
DOI：
10.4049/jimmunol.1100013
发表时间：
2011-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Peña G;Cai B;Ramos L;Vida G;Deitch EA;Ulloa L
通讯作者：
Ulloa L
影响因子：
64.8
作者：
GORISSEN, H;LADURON, P
通讯作者：
LADURON, P
影响因子：
29.4
作者：
Van Westerloo, David J.;Giebelen, Ilona A.;Van der Poll, T.
通讯作者：
Van der Poll, T.
影响因子：
158.5
作者：
PULLAN, RD;RHODES, J;SAWE, U
通讯作者：
SAWE, U
DOI：
10.4049/jimmunol.1003722
发表时间：
2011-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Vida G;Peña G;Deitch EA;Ulloa L
通讯作者：
Ulloa L