Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation
Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation
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DOI：
10.1016/s1566-0702(00)00233-2
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发表时间：
2000-12-20
影响因子：
2.7
通讯作者：
Tracey, KJ
中科院分区：
文献类型：
--
作者：
Borovikova, LV;Ivanova, S;Tracey, KJ
CNI - 1493是一种有效的抗炎剂，它能使巨噬细胞失活并抑制促炎介质的合成。本研究的目的是确定中枢神经系统（CNS）和传出迷走神经信号在CNI - 1493介导的外周急性炎症调节中的作用。在接受急性炎症标准模型（皮下注射角叉菜胶）的麻醉大鼠中，CNI - 1493分别通过脑室内（i.c.v.，0.1 - 1000 ng/kg）或静脉内（i.v.，5 mg/kg）给药。脑室内给予CNI - 1493显著抑制角叉菜胶诱导的足肿胀，即使剂量比产生全身效应所需剂量至少低6个对数级。双侧颈迷走神经切断术或阿托品阻断（1 mg/kg/h）消除了CNI - 1493（1μg/kg，i.c.v.或5 mg/kg，i.v.）的抗炎作用，表明CNI - 1493的活性需要完整的迷走神经。对传出迷走神经活动的记录显示，在CNI - 1493给药（5 mg/kg，i.v.）后3 - 4分钟开始放电频率增加，并持续10 - 14分钟（对照活动 = 87±5.4脉冲/秒，而CNI - 1493诱导的活动 = 229±6.7脉冲/秒）。通过对切断的外周迷走神经进行20分钟（角叉菜胶给药前10分钟和给药后10分钟）的电刺激（5 V，2 ms，1 Hz）来调节传出迷走神经活动，也可阻止急性炎症的发展。在角叉菜胶注射部位局部给予迷走神经递质乙酰胆碱（4μg/kg，s.c.）或胆碱能激动剂也可抑制急性炎症。这些结果现在确定了传出迷走神经活动在介导抗炎剂的中枢作用方面以前未被认识到的作用。（C）2000年由爱思唯尔科学出版社（Elsevier Science B.V.）出版
CNI-1493 is a potent anti-inflammatory agent, which deactivates macrophages and inhibits the synthesis of proinflammatory mediators. The objective of the present study was to identify the role of the central nervous system (CNS) and efferent vagus nerve signaling in CNI-1493-mediated modulation of acute inflammation in the periphery. CNI-1493 was administered either intracerebroventricularly (i.c.v., 0.1-1000 ng/kg) or intravenously (i.v., 5 mg/kg) in anesthetized rats subjected to a standard model of acute inflammation (subcutaneous (s.c.) injection of carrageenan). I.c.v. CNI-1493 significantly suppressed carrageenan-induced paw edema, even in doses at least 6-logs lower than those required for a systemic effect. Bilateral cervical vagotomy or atropine blockade (I mg/kg/h) abrogated the anti-inflammatory effects of CNI-1493 (1 mug/kg, i.c.v. or 5 mg/kg, i.v.), indicating that the intact vagus nerve is required for CNI-1493 activity. Recording of the efferent vagus nerve activity revealed an increase in discharge rate starting at 3-4 min after CNI-1493 administration (5 mg/kg, i.v.) and lasting for 10-14 min (control activity=87+/-5.4 impulses/s versus CNI-1493-induced activity=229+/-6.7 impulses/s). Modulation of efferent vagus nerve activity by electrical stimulation (5 V, 2 ms, 1 Hz) of the transected peripheral vagus nerve for 20 min (10 min before carrageenan administration and 10 min after) also prevented the development of acute inflammation. Local administration of the vagus nerve neurotransmitter, acetylcholine (4 mug/kg, s.c.), or cholinergic agonists into the site of carrageenan-injection also inhibited acute inflammation. These results now identify a previously unrecognized role of efferent vagus nerve activity in mediating the central action of an anti-inflammatory agent. (C) 2000 Published by Elsevier Science B.V.