Institute of Neuroscience, Carleton University, Canada.
Brain Behav Immun. 2011 Mar;25(3):468-82. doi: 10.1016/j.bbi.2010.11.008. Epub 2010 Nov 18.
The impact of inflammatory immune activation on behavioral and physiological processes varies with antecedent stressor experiences. We assessed whether immune activation would differentially influence such outcomes as a function of stressor reactivity related to genetic differences. To this end, we assessed the influence of a social stressor (exposure to a dominant mouse) in combination with an acute immune challenge on behavior and on peripheral and central cytokines in stressor-reactive BALB/cByJ mice and the less reactive C57BL/6ByJ strain. As C57BL/6ByJ and BALB/cByJ mice are highly T helper type-1 (Th1) and Th2 responsive, respectively, the stressor effects were assessed in response to different challenges, namely the viral analogue poly I:C and the bacterial endotoxin lipopolysaccharide (LPS). The stressor enhanced the effects of LPS on sickness behaviors and plasma corticosterone particularly in BALB/cByJ mice, whereas the effects of poly I:C, which primarily affects Th1 processes, were not augmented by the stressor. As well, the stressor increased circulating cytokines in LPS treated C57BL/6ByJ mice, whereas the effects of poly I:C were diminished. Finally, like circulating cytokines, mRNA expression of pro-inflammatory cytokines within the prefrontal cortex and hippocampus varied with the mouse strain and with the stressor experience, and with the specific cytokine considered. Together, the experiments indicated that the impact of stressors vary with the nature of the immune challenge to which animals had been exposed. Moreover, given the diversity of the stressor effects on central and peripheral processes, it seems likely that the cytokine changes, HPA activity and sickness operate through independent mechanisms.
炎症免疫激活对行为和生理过程的影响因先前的应激体验而异。我们评估了免疫激活是否会根据与遗传差异相关的应激反应性的不同，对这些结果产生不同的影响。为此，我们评估了社交应激源（暴露于优势小鼠）与急性免疫挑战相结合，对应激反应性 BALB/cByJ 小鼠和反应性较低的 C57BL/6ByJ 品系的行为以及外周和中枢细胞因子的影响。由于 C57BL/6ByJ 和 BALB/cByJ 小鼠分别高度响应 T 辅助细胞 1（Th1）和 Th2，因此，应激源的影响是根据不同的挑战来评估的，即病毒类似物聚肌胞和细菌内毒素脂多糖（LPS）。应激源增强了 LPS 对疾病行为和血浆皮质酮的影响，特别是在 BALB/cByJ 小鼠中，而聚肌胞的影响（主要影响 Th1 过程）则不受应激源的增强。同样，应激源增加了 LPS 处理的 C57BL/6ByJ 小鼠中的循环细胞因子，而聚肌胞的影响则减弱。最后，与循环细胞因子一样，前额叶皮层和海马体中促炎细胞因子的 mRNA 表达也随小鼠品系和应激源体验以及所考虑的特定细胞因子而变化。总之，实验表明，应激源的影响因动物所暴露的免疫挑战的性质而异。此外，鉴于应激源对中枢和外周过程的影响的多样性，似乎细胞因子变化、HPA 活动和疾病通过独立的机制起作用。
