Curtin Niamh M, Mills Kingston H G, Connor Thomas J
Neuroimmunology Research Group, Department of Physiology, School of Medicine & Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.
Brain Behav Immun. 2009 Mar;23(3):371-9. doi: 10.1016/j.bbi.2008.12.010. Epub 2009 Jan 3.
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 LPS 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 beta-adrenoceptor antagonist propranolol. Similarly, pre-treatment of mice with the peripherally acting beta-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.
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的强效诱导剂，这增加了细胞因子IL-10家族可能是应激诱导免疫抑制的关键介质的可能性。在本研究中，我们检测了心理压力（束缚应激）对小鼠脾脏中IL-10以及新型IL-10家族成员IL-19、IL-20和IL-24表达的影响，这些小鼠在体内经脂多糖（LPS）攻击后进行检测。我们发现，暴露于应激源显著增强了LPS诱导的IL-10表达。同样，LPS诱导了IL-19的表达，而束缚应激使其显著增强。相比之下，LPS或应激对IL-24的表达没有显著改变，并且在生理盐水或LPS处理的动物体内，IL-20的表达在很大程度上无法检测到。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β-肾上腺素能受体拮抗剂普萘洛尔预处理可阻断去甲肾上腺素诱导这些细胞因子表达的能力。同样，用外周作用的β-肾上腺素能受体拮抗剂纳多洛尔预处理小鼠可完全阻断应激诱导的IL-10和IL-19 mRNA表达增加。最后，用苯二氮䓬类抗焦虑药氯氮䓬预处理可防止应激诱导的IL-10和IL-19表达增加。综上所述，这些数据表明心理压力通过β-肾上腺素能受体激活诱导IL-10及其同系物IL-19的表达，而抗焦虑药氯氮䓬处理可防止应激诱导这些细胞因子的表达。这些发现表明，应激增强了免疫抑制细胞因子的产生，这可能影响与应激相关的疾病进程。
