Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alta., Canada.
Neuroimmunomodulation. 2010;17(4):229-39. doi: 10.1159/000290039. Epub 2010 Mar 5.
BACKGROUND/AIMS: Neonatal stress induces permanent physiological changes that may influence the immune system. Early-life stress increases asthma disease severity in children. We investigated the effects of early-life stress on allergic airway inflammation using a murine model of asthma coupled to maternal separation as an early-life stress stimulus.
Maternally separated (MS) and unseparated control (CON) mice were sensitized with ovalbumin (OVA) beginning at day 31 after birth.
Challenging mice with OVA increased airway hyperresponsiveness (AHR) and the number of inflammatory cells recovered in the bronchoalveolar lavage (BAL), compared to saline-challenged mice. Challenging MS mice with OVA resulted in less total inflammatory cells, eosinophils, interferon-gamma, and interleukin-4 in BAL compared to CON mice. However, MS mice challenged with OVA exhibited AHR similar to CON mice challenged with OVA. In contrast, an enhanced stress protocol (MS+) involving removal of pups from their home cages following the removal of the dam resulted in inflammatory cell accumulation and cytokine levels in the BAL similar to CON mice and higher than MS mice.
These findings indicate that the effect of early-life psychological factors on the development of airway inflammatory diseases such as asthma is very complex and depends on the quality of the psychological stress stimulus.
背景/目的：新生儿应激会引起永久性的生理变化，可能会影响免疫系统。儿童期早期生活压力会增加哮喘的严重程度。我们使用哮喘的小鼠模型和母亲分离作为早期生活应激刺激，研究了早期生活应激对过敏性气道炎症的影响。
从出生后第 31 天开始，对分离（MS）和未分离对照（CON）的母鼠进行卵清蛋白（OVA）致敏。
与盐水刺激的小鼠相比，OVA 刺激增加了气道高反应性（AHR）和支气管肺泡灌洗液（BAL）中回收的炎症细胞数量。与 CON 小鼠相比，MS 小鼠用 OVA 刺激后 BAL 中的总炎症细胞、嗜酸性粒细胞、干扰素-γ和白细胞介素-4减少。然而，OVA 刺激的 MS 小鼠的 AHR 与 OVA 刺激的 CON 小鼠相似。相比之下，一种增强的应激方案（MS+）涉及在母鼠离开后从其巢箱中取出幼鼠，导致 BAL 中的炎症细胞积聚和细胞因子水平类似于 CON 小鼠，高于 MS 小鼠。
这些发现表明，早期心理因素对哮喘等气道炎症性疾病发展的影响非常复杂，取决于心理应激刺激的质量。
