Plasma IL-12 levels are suppressed in vivo by stress and surgery through endogenous release of glucocorticoids and prostaglandins but not catecholamines or opioids.
Plasma IL-12 levels are suppressed in vivo by stress and surgery through endogenous release of glucocorticoids and prostaglandins but not catecholamines or opioids.
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DOI：
10.1016/j.psyneuen.2013.12.001
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发表时间：
2014-04
影响因子：
3.7
通讯作者：
Ben-Eliyahu, Shamgar
中科院分区：
文献类型：
--
作者：
Shaashua, Lee;Rosenne, Ella;Neeman, Elad;Sorski, Liat;Sominsky, Luba;Matzner, Pini;Page, Gayle G.;Ben-Eliyahu, Shamgar
IL-12是一种重要的Th 1分化因子和白细胞激活因子。大量研究表明，IL-12的产生受到许多应激因素的抑制，包括肾上腺素、儿茶酚胺、糖皮质激素和阿片类药物，但在体外和人工白细胞活化的背景下，不模拟体内环境。在最近的一项研究中，我们报告了行为应激和手术对血浆IL-12水平的体内抑制。本研究旨在阐明幼稚F344大鼠这种现象的神经内分泌机制。为此，使用肾上腺切除术和特定拮抗剂的给药，靶向上述应激因素。结果表明，皮质酮和白藜芦醇是应激和手术的IL-12抑制作用的主要介质，显然是通过直接抑制白细胞IL-12的产生。手术后，内源性洋地黄素主要通过升高皮质酮水平发挥作用。重要的是，应激诱导的肾上腺素或阿片类药物释放对血浆IL-12水平没有影响，而肾上腺素的药理学给药通过升高皮质酮水平降低血浆IL-12水平。最后，一项全血体外研究表明，在非刺激的白细胞中，野牡丹素和皮质酮（而不是肾上腺素）抑制IL-12的产生，并且在CpG-C诱导的IL-12产生的背景下，只有皮质酮才能抑制IL-12的产生。总体而言，研究结果重申了体外或体内药理学研究的结果不能表明应激/手术条件下内源性释放的应激激素的影响。在此，皮质酮和肾上腺素，而不是儿茶酚胺或阿片类药物，是应激和手术对其他未处理动物体内血浆IL-12水平抑制作用的关键介质。
IL-12 is a prominent Th1 differentiator and leukocyte activator. Ample studies showed suppression of IL-12 production by numerous stress factors, including prostaglandins, catecholamines, glucocorticoids, and opioids, but did so in vitro and in the context of artificial leukocyte activation, not simulating the in vivo setting. In a recent study we reported in vivo suppression of plasma IL-12 levels by behavioral stress and surgery. The current study aims to elucidate neuroendocrine mechanisms underlying this phenomenon in naïve F344 rats. To this end, both adrenalectomy and administration of specific antagonists were used, targeting the aforementioned stress factors. The results indicated that corticosterone and prostaglandins are prominent mediators of the IL-12-suppressing effects of stress and surgery, apparently through directly suppressing leukocyte IL-12 production. Following surgery, endogenous prostaglandins exerted their effects mainly through elevating corticosterone levels. Importantly, stress-induced release of epinephrine or opioids had no impact on plasma IL-12 levels, while pharmacological administration of epinephrine reduced plasma IL-12 levels by elevating corticosterone levels. Last, a whole blood in vitro study indicated that prostaglandins and corticosterone, but not epinephrine, suppressed IL-12 production in non-stimulated leukocytes, and only corticosterone did so in the context of CpG-C-induced IL-12 production. Overall, the findings reiterate the notion that results from in vitro or pharmacological in vivo studies cannot indicate the effects of endogenously released stress hormones under stress/surgery conditions. Herein, corticosterone and prostaglandins, but not catecholamines or opioids, were key mediators of the suppressive effect of stress and surgery on in vivo plasma IL-12 levels in otherwise naïve animals.
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影响因子：
2.4
作者：
Ben-Eliyahu, S;Shakhar, G;Shakhar, K
通讯作者：
Shakhar, K
影响因子：
3.6
作者：
DETURCK, KH;VOGEL, WH
通讯作者：
VOGEL, WH
影响因子：
6.1
作者：
HEIKINHEIMO, O;PESONEN, U;LAHTEENMAKI, P
通讯作者：
LAHTEENMAKI, P
DOI：
10.1111/j.1365-2125.1986.tb02849.x
发表时间：
1986-01-01
影响因子：
3.4
作者：
KAYE, B;CUSSANS, NJ;REID, JL
通讯作者：
REID, JL
DOI：
10.1164/ajrccm/154.2_pt_2.s21
发表时间：
1996-08-01
影响因子：
24.7
作者：
Barnes, PJ
通讯作者：
Barnes, PJ