Institute of Behavioural Physiology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.
Institute of Behavioural Physiology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany; Behavioural Sciences, Faculty of Agricultural and Environmental Sciences, University of Rostock, Justus-von-Liebig-Weg 6, 18059 Rostock, Germany.
Brain Behav Immun. 2018 Feb;68:274-287. doi: 10.1016/j.bbi.2017.10.026. Epub 2017 Nov 2.
Exposure to psychosocial stress can have a profound impact on immune reactivity and health mediated by hypothalamic-pituitaryadrenal (HPA) axis activation. However, current knowledge regarding the mechanisms involved in cross-sensitization between stress and the immune system is limited. Here, we investigated the effects of a single social isolation followed by repeated oral Escherichia coli (E. coli) applications on cortisol, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), haptoglobin and C-reactive protein (CRP) concentrations in the blood; on clinical signs of disease; and on mRNA expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 11β-HSD2), TNF-α and IL-6 in the hypothalamus, prefrontal cortex (PFC) and spleen of 7-, 21- and 35-day-old piglets. Additionally, the protein levels of splenic TNF-α and IL-6 were analyzed. Non-isolated, E. coli-challenged piglets served as a control. Social isolation for 4 h induced a rise in the plasma cortisol concentrations immediately after social treatment and after repeated E. coli applications in isolated compared to non-isolated piglets. The circulating TNF-α concentration was not affected by social treatment. Furthermore, previously isolated piglets showed a higher frequency of signs of disease in response to E. coli challenge than non-isolated piglets, while the haptoglobin and CRP concentrations did not significantly differ between social treatments. In the brain, 11β-HSD1, 11β-HSD2 and IL-6 mRNA expression in the hypothalamus and GR, and 11β-HSD1 and 11β-HSD2 mRNA expression in the PFC were higher in isolated, E. coli-challenged piglets than in the corresponding controls. Moreover, isolated piglets also displayed higher MR, 11β-HSD1 and IL-6 mRNA expression levels and TNF-α concentrations in the spleen. The stress-induced alterations in the hypothalamus and spleen were particularly pronounced in younger piglets. The present findings may contribute to a better understanding of the complex interplay between early psychological stress and an increased risk of disease and might also have implications on aspects of the health and welfare of farm animals and humans.
心理社会应激会通过下丘脑-垂体-肾上腺（HPA）轴的激活对免疫反应和健康产生深远影响。然而，目前对于应激和免疫系统之间交叉敏感化所涉及的机制的了解有限。在这里，我们研究了单次社会隔离后反复口服大肠杆菌（E. coli）应用对血液中皮质醇、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、触珠蛋白和 C 反应蛋白（CRP）浓度的影响；对疾病临床症状的影响；以及对 7、21 和 35 日龄仔猪下丘脑、前额叶皮质（PFC）和脾脏中糖皮质激素受体（GR）、盐皮质激素受体（MR）、11β-羟类固醇脱氢酶 1 和 2（11β-HSD1 和 11β-HSD2）、TNF-α 和 IL-6 的 mRNA 表达的影响。此外，还分析了脾脏中 TNF-α 和 IL-6 的蛋白水平。未隔离、大肠杆菌挑战的仔猪作为对照。4 小时的社会隔离会导致隔离仔猪在社会处理后立即以及在反复接受大肠杆菌应用后血浆皮质醇浓度升高。循环 TNF-α浓度不受社会处理的影响。此外，与未隔离仔猪相比，先前隔离的仔猪在大肠杆菌挑战时表现出更高的疾病症状频率，而触珠蛋白和 CRP 浓度在社会处理之间没有显著差异。在大脑中，下丘脑和 PFC 中的 11β-HSD1、11β-HSD2 和 IL-6 mRNA 表达以及 GR 中的 11β-HSD1 和 11β-HSD2 mRNA 表达在隔离、大肠杆菌挑战的仔猪中高于相应的对照。此外，隔离仔猪的脾脏中还显示出更高的 MR、11β-HSD1 和 IL-6 mRNA 表达水平和 TNF-α浓度。在较小的仔猪中，下丘脑和脾脏中的应激诱导改变更为明显。这些发现可能有助于更好地理解早期心理应激与疾病风险增加之间的复杂相互作用，并可能对农场动物和人类的健康和福利方面产生影响。
