Division of Oral Biology, The Ohio State University College of Dentistry, Columbus, OH 43210, USA.
Brain Behav Immun. 2012 Oct;26(7):1150-9. doi: 10.1016/j.bbi.2012.07.011. Epub 2012 Jul 24.
During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of different cell types. The impact of the SNS on the immune modulation of social defeat has not been examined. The following studies were designed to determine whether SNS activation during social disruption stress (SDR) influences anxiety-like behavior as well as the activation, priming, and glucocorticoid resistance of splenocytes after social stress. CD-1 mice were exposed to one, three, or six cycles of SDR and HPLC analysis of the plasma and spleen revealed an increase in catecholamines. After six cycles of SDR the open field test was used to measure behaviors characteristic of anxiety and indicated that the social defeat induced increase in anxiety-like behavior was blocked by pre-treatment with the β-adrenergic antagonist propranolol. Pre-treatment with the β-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic-pituitary-adrenal axis. In addition to anxiety-like behavior the SDR induced splenomegaly and increase in plasma IL-6, TNFα, and MCP-1 were each reversed by pre-treatment with propranolol. Furthermore, flow cytometric analysis of cells from propranolol pretreated mice reduced the SDR-induced increase in the percentage of CD11b(+) splenic macrophages and significantly decreased the expression of TLR2, TLR4, and CD86 on the surface of these cells. In addition, supernatants from 18h LPS-stimulated ex vivo cultures of splenocytes from propranolol-treated SDR mice contained less IL-6. Likewise propranolol pre-treatment abrogated the glucocorticoid insensitivity of CD11b(+) cells ex vivo when compared to splenocytes from SDR vehicle-treated mice. Together, this study demonstrates that the immune activation and priming effects of SDR result, in part, as a consequence of SNS activation.
在生理或心理压力下，交感神经系统 (SNS) 产生的儿茶酚胺调节免疫系统。先前的研究报告表明，β-肾上腺素能受体 (βAR) 的激活介导儿茶酚胺的作用，并增加许多不同细胞类型中促炎细胞因子的产生。SNS 对社交挫败引起的免疫调节的影响尚未被研究。以下研究旨在确定在社交中断应激 (SDR) 期间 SNS 激活是否会影响焦虑样行为，以及社交应激后脾细胞的激活、启动和糖皮质激素抵抗。CD-1 小鼠暴露于 SDR 一个、三个或六个周期，血浆和脾脏的 HPLC 分析显示儿茶酚胺增加。在 SDR 六个周期后，使用开阔场测试测量焦虑特征的行为，表明社交挫败诱导的焦虑样行为增加被β-肾上腺素能拮抗剂普萘洛尔预处理阻断。β-肾上腺素能拮抗剂普萘洛尔预处理并未显著改变皮质酮水平，表明下丘脑-垂体-肾上腺轴的激活没有差异。除了焦虑样行为外，SDR 还诱导脾肿大和血浆 IL-6、TNFα 和 MCP-1 增加，这些均被普萘洛尔预处理逆转。此外，普萘洛尔预处理小鼠的细胞流式细胞术分析降低了 SDR 诱导的 CD11b(+) 脾巨噬细胞百分比增加，并显著降低了这些细胞表面 TLR2、TLR4 和 CD86 的表达。此外，来自 SDR 应激下经普萘洛尔预处理的小鼠的 LPS 刺激的脾细胞 18 小时体外培养上清液中含有更少的 IL-6。同样，与 SDR 载体处理的小鼠的脾细胞相比，普萘洛尔预处理消除了 CD11b(+) 细胞的糖皮质激素不敏感性。总之，这项研究表明，SDR 的免疫激活和启动作用部分是由于 SNS 激活的结果。
