Low- versus high-baseline epinephrine output shapes opposite innate cytokine profiles: presence of Lewis- and Fischer-like neurohormonal immune phenotypes in humans?
Low- versus high-baseline epinephrine output shapes opposite innate cytokine profiles: presence of Lewis- and Fischer-like neurohormonal immune phenotypes in humans?
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DOI：
10.4049/jimmunol.181.3.1737
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发表时间：
2008-08-01
期刊：
影响因子：
--
通讯作者：
Wilder RL
中科院分区：
文献类型：
--
作者：
Elenkov IJ;Kvetnansky R;Hashiramoto A;Bakalov VK;Link AA;Zachman K;Crane M;Jezova D;Rovensky J;Dimitrov MA;Gold PW;Bonini S;Fleisher T;Chrousos GP;Wilder RL
已知在免疫系统内操作的免疫遗传机制影响细胞因子谱和疾病易感性。然而，个体的神经激素背景在这些过程中的作用仍然不确定。激素失衡在免疫相关疾病中有记载，但尚不清楚这是否代表与特定神经激素免疫表型相关的继发现象或原发性“缺陷”。我们报告说，在一个大的健康人的亚群的基线肾上腺素输出（但不是皮质醇和性类固醇激素）与促炎症和抗炎细胞因子的生产呈负相关。因此，低肾上腺素分泌物与高肾上腺素分泌物相比，LPS离体诱导的TNF-α和IL-12产生高2至5倍，但IL-10产生低2倍。在替代环境中，我们发现刘易斯与费舍尔近交系大鼠的基线水平较低，应激诱导的肾上腺素反应明显减弱，但TNF-α水平较高。此外，β肾上腺素受体激动剂异丙肾上腺素抑制LPS诱导的TNF-α产生，在刘易斯大鼠中的作用比在费舍尔大鼠中更明显。在人单核细胞中，肾上腺素和β2肾上腺素受体激动剂非诺特罗有效抑制LPS诱导的TNF-α和IL-12，但刺激IL-10的产生。能够体外抑制IL-12产生的激素的效力顺序为：肾上腺素>去甲肾上腺素> = 1，25-（OH）2维生素D3>氢化可的松。这表明，基线肾上腺素条件细胞因子的反应性，并通过这种机制内在的低或高活性的肾上腺髓质在一些人可能会形成相反的细胞因子的配置文件。由于刘易斯和Fischer大鼠对实验性免疫疾病具有相反的易感性，这表明平行的人类表型可能与对感染和免疫/炎症相关病症的不同反应性和易感性有关。
Immunogenetic mechanisms operating within the immune system are known to influence cytokine profiles and disease susceptibility. Yet the role of the individual’s neurohormonal background in these processes remains undefined. Hormonal imbalances are documented in immune-related diseases, but it is unclear whether this represents a secondary phenomenon or a primary “defect” related to specific neurohormonal immune phenotype(s). We report that in a large subpopulation of healthy humans the baseline epinephrine output (but not cortisol and sex steroid hormones) correlated inversely with proinflammatory and positively with anti-inflammatory cytokine production. Thus, low vs high epinephrine excretors had a 2- to 5-fold higher TNF-α and IL-12 production but 2-fold lower IL-10 production induced by LPS ex vivo. In alternative settings, we found low baseline levels and profoundly blunted stress-induced epinephrine responses but high TNF-α levels in Lewis vs Fischer inbred rats. Additionally, isoproterenol, a β adrenoreceptor agonist suppressed LPS-induced TNF-α production, with more pronounced effect in Lewis than in Fischer rats. In human monocytes, epinephrine and the β2 adrenoreceptor agonist fenoterol potently inhibited LPS-induced TNF-α and IL-12, but stimulated IL-10 production. The order of potency for hormones able to inhibit IL-12 production ex vivo was: epinephrine > norepinephrine > = 1,25-(OH)2 vitamin D3, > hydrocortisone. This indicates that baseline epinephrine conditions cytokine responsiveness and through this mechanism intrinsic hypo- or hyperactive adrenal medullas in some individuals may shape opposite cytokine profiles. Since Lewis and Fischer rats have opposite susceptibility to experimental immunological diseases, this suggests that the parallel human phenotypes could be linked to differing responsiveness and susceptibility to infections and immune/inflammatory-related conditions.
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影响因子：
5.4
作者：
Kempf, MC;Cesbron-Delauw, MF;Sutton, P
通讯作者：
Sutton, P
影响因子：
4.4
作者：
Cobelens, PM;Kavelaars, A;Heijnen, CJ
通讯作者：
Heijnen, CJ
DOI：
10.1164/ajrccm.153.3.8630548
发表时间：
1996-03-01
影响因子：
24.7
作者：
Entzian, P;Linnemann, K;Zabel, P
通讯作者：
Zabel, P
DOI：
10.1073/pnas.221134198
发表时间：
2001-10-23
影响因子：
11.1
作者：
Cole, SW;Naliboff, BD;Zack, JA
通讯作者：
Zack, JA
影响因子：
15.9
作者：
PaninaBordignon, P;Mazzeo, D;Sinigaglia, F
通讯作者：
Sinigaglia, F