Central lipopolysaccharide elevates plasma IL-6 concentration by an alpha-adrenoreceptor-mediated mechanism
Central lipopolysaccharide elevates plasma IL-6 concentration by an alpha-adrenoreceptor-mediated mechanism
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DOI：
10.1152/ajpregu.1997.272.6.r1880
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发表时间：
1997-06-01
影响因子：
2.8
通讯作者：
Johnson, RW
中科院分区：
文献类型：
--
作者：
Finck, BN;Dantzer, R;Johnson, RW
脑室内注射脂多糖（LPS）后，高循环水平的白细胞介素-6（IL-6）是明显的。为了研究中枢诱导的IL-6产生的途径，在本研究中，我们评估了外周给予特异性α-肾上腺素能受体拮抗剂对中枢给予LPS诱导的IL-6产生和高脂血症的影响。在第一项研究中，成年雄性Wistar-Furth大鼠脑室内注射LPS。中心注射LPS以剂量依赖性方式增加血浆IL-6和甘油三酯（TG）。为了确定LPS是否通过α-肾上腺素受体机制增加血浆IL-6和TG，用载体、酚妥拉明（α（1）-和α（2）-受体拮抗剂）、哌唑嗪（α（1）-受体拮抗剂）或育亨宾（α（2）-受体拮抗剂）对大鼠进行腹膜内预处理。30分钟后，大鼠侧脑室注射LPS。而哌唑嗪和育亨宾减弱LPS引起的血浆IL-6的增加，酚妥拉明完全阻断中枢LPS的外周效应。这些数据表明，增加交感神经活动和随后激活的α（1）-和α（2）-肾上腺素能受体是重要的控制外周代谢和内分泌系统时，炎症刺激存在于大脑中。
High circulating levels of interleukin-6 (IL-6) are evident after intracerebroventricular injection of lipopolysaccharide (LPS). To investigate the pathway of centrally induced IL-6 production, in the present study we evaluated the effects of specific alpha-adrenergic receptor antagonists administered peripherally on IL-6 production and hypertriglyceridemia induced by LPS administered centrally. In the first study, adult male Wistar-Furth rats were injected intracerebroventricularly with LPS. Centrally injected LPS increased plasma IL-6 and triglycerides (TG) in a dose-dependent fashion. To determine if LPS increased plasma IL-6 and TG through an alpha-adrenoreceptor mechanism, rats were pretreated intraperitoneally with either vehicle, phentolamine (alpha(1)- and alpha(2)-receptor antagonist), prazosin (alpha(1)-receptor antagonist), or yohimbine (alpha(2)-receptor antagonist). Thirty minutes later, rats were injected intracerebroventricularly with LPS. Whereas prazosin and yohimbine attenuated the increases in plasma IL-6 caused by LPS, phentolamine completely blocked the peripheral effects of central LPS. These data suggest that increased sympathetic activity and subsequent activation of alpha(1)- and alpha(2)-adrenergic receptors are important for controlling peripheral metabolic and endocrine systems when inflammatory stimuli are present in the brain.