Psychological stress increases expression of IL-10 and its homolog IL-19 via β-adrenoceptor activation: Reversal by the anxiolytic chlordiazepoxide
Psychological stress increases expression of IL-10 and its homolog IL-19 via β-adrenoceptor activation: Reversal by the anxiolytic chlordiazepoxide
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DOI：
10.1016/j.bbi.2008.12.010
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发表时间：
2009-03-01
影响因子：
15.1
通讯作者：
Connor, Thomas J.
中科院分区：
文献类型：
--
作者：
Curtin, Niamh M.;Mills, Kingston H. G.;Connor, Thomas J.
我们实验室最近的研究表明，心理压力是抗炎细胞因子白细胞介素 (IL)-10 的有效诱导剂，这提高了细胞因子 IL-10 家族可能是压力诱导的免疫抑制的关键介质的可能性。在这项研究中，我们研究了心理压力（约束压力）对 IL-10 和新的 IL-10 家族成员 IL-19 表达的影响。体内脂多糖 (LPS) 攻击后小鼠脾脏中的 IL-20 和 IL-24。我们发现应激源暴露显着增强了 LPS 诱导的 IL-10 表达。类似地，IL-19 表达是由 LPS 诱导的，并且这种表达通过束缚应激显着增强。相比之下，LIPS或应激不会显着改变IL-24的表达，并且在盐水或LPS处理的动物体内基本上检测不到IL-20的表达。与交感神经系统（SNS）激活在应激诱导的免疫调节中的作用一致，交感神经递质去甲肾上腺素增加了LPS诱导的脾细胞和树突状细胞中IL-10和IL-19的表达，并且去甲肾上腺素诱导这些细胞因子表达的能力被β-肾上腺素受体拮抗剂普萘洛尔预处理所阻断。同样，用外周作用的β-肾上腺素受体拮抗剂纳多洛尔对小鼠进行预处理，完全阻断了应激诱导的IL-10和IL-19 mRNA表达的增加。最后，使用苯二氮卓类抗焦虑药利眠宁进行预处理可防止应激诱导的 IL-10 和 IL-19 表达增加。总而言之，这些数据表明，心理压力通过激活 β-肾上腺素受体诱导 IL-10 及其同源物 IL-19 的表达，并且用抗焦虑药利眠宁治疗可以阻止压力诱导这些细胞因子的能力。研究结果表明，压力会增强免疫抑制细胞因子的产生，这可能会影响与压力相关的疾病过程。 (C) 2008 Elsevier Inc. 保留所有权利。
Recent studies from our laboratory indicate that psychological stress is a potent inducer of the anti-inflammatory cytokine interleukin (IL)-10, raising the possibility that the IL-10 family of cytokines may be key mediators of stress-induced immunosuppression. In this study we examined the impact of psychological stress (restraint stress) on expression of IL-10, and the novel IL-10 family members IL-19. IL-20 and IL-24 in mouse spleen following an in vivo challenge with lipopolysaccharide (LPS). We found that stressor exposure significantly augmented LPS-induced IL-10 expression. Similarly, IL-19 expression was induced by LPS, and this was significantly enhanced by restraint stress. In contrast, expression of IL-24 was not significantly altered by LIPS or stress, and expression of IL-20 was largely not detectable in vivo in either saline or LPS-treated animals. Consistent with a role for sympathetic nervous system (SNS) activation in stress-induced immune regulation, the sympathetic neurotransmitter noradrenaline increased LPS-induced IL-10 and IL-19 expression in splenocytes and dendritic cells, and the ability of noradrenaline to induce expression of these cytokines was blocked by pre-treatment with the p-adrenoceptor antagonist propranolol. Similarly, pre-treatment of mice with the peripherally acting p-adrenoceptor antagonist nadolol completely blocked the stress-induced increase in IL-10 and IL-19 mRNA expression. Finally, pre-treatment with the benzodiazepine anxiolytic chlordiazepoxide prevented the stress-induced increase in IL-10 and IL-19 expression. Taken together, these data demonstrate that psychological stress induces expression of the IL-10 and its homolog IL-19 via activation of beta-adrenoceptors, and the ability of stress to induce these cytokines is prevented by treatment with the anxiolytic chlordiazepoxide. The findings suggest that stress enhances the production of immunosuppressive cytokines, which may impact on stress-related disease processes. (C) 2008 Elsevier Inc. All rights reserved.