Dobbs C M, Feng N, Beck F M, Sheridan J F
Department of Medical Microbiology and Immunology, College of Medicine, Ohio State University, Columbus 43210, USA.
J Immunol. 1996 Sep 1;157(5):1870-7.
A murine model of influenza viral infection was used to examine the neuroendocrine regulation of cytokine production. Restraint stress (RST) was used to activate the hypothalamic-pituitary-adrenal axis and elevate corticosterone (CORT) levels in influenza A/Puerto Rico/8/34 (PR8) virus-infected C57BL/6 mice. The type II glucocorticoid receptor antagonist RU486 was used to specifically examine the modulation of PR8 virus-specific cytokine responses by CORT. RST suppressed the PR8 virus- specific production of Th1-type (IL-2 and IFN-gamma) and Th2-type IL-10) cytokines by cells from the regional lymph nodes and spleens. In addition, IL-6 production by splenocytes was inhibited by RST; however, IL-6 production by cells from the regional lymph nodes was enhanced. Treatment of mice with RU486 prevented the effects of RST, suggesting that the RST-induced alterations in cytokine responses were mediated by CORT. Furthermore, CORT was shown to inhibit the PR8 virus-specific production of both Thl-type and Th2-type cytokines in vitro at doses corresponding to the physiologic range of free plasma CORT following hypothalamic-pituitary-adrenal axis activation.
利用流感病毒感染的小鼠模型来研究细胞因子产生的神经内分泌调节。采用束缚应激（RST）激活甲型流感病毒/波多黎各/8/34（PR8）感染的C57BL/6小鼠的下丘脑-垂体-肾上腺轴并提高皮质酮（CORT）水平。使用II型糖皮质激素受体拮抗剂RU486来专门研究CORT对PR8病毒特异性细胞因子反应的调节作用。RST抑制了来自局部淋巴结和脾脏的细胞对PR8病毒特异性产生的Th1型（IL-2和IFN-γ）和Th2型（IL-10）细胞因子。此外，RST抑制了脾细胞产生IL-6；然而，却增强了局部淋巴结细胞产生IL-6的能力。用RU486处理小鼠可防止RST的作用，这表明RST诱导的细胞因子反应改变是由CORT介导的。此外，在体外，对应于下丘脑-垂体-肾上腺轴激活后游离血浆CORT的生理范围剂量，CORT可抑制Th1型和Th2型细胞因子对PR8病毒的特异性产生。
