Postnatal life events affect the severity of asthmatic airway inflammation in the adult rat
Postnatal life events affect the severity of asthmatic airway inflammation in the adult rat
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DOI：
10.4049/jimmunol.180.6.3919
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发表时间：
2008-03-15
影响因子：
4.4
通讯作者：
von Hoersten, Stephan
中科院分区：
文献类型：
--
作者：
Kruschinski, Carsten;Skripuletz, Thomas;von Hoersten, Stephan
遗传和卫生因素影响哮喘易感性。在自身免疫性疾病和炎症性疾病中，心理社会环境的额外影响已被证明也可能在哮喘中发挥作用。在这项研究中，不同的早期出生后的压力对OVA诱导的哮喘模型的影响进行了测试，在成年期。Fischer 344大鼠在出生后的前4周接受重复处理刺激（HA）、母体分离（MS）或不受干扰。行为差异的特点是在4个月的年龄。在5月龄时，观察免疫细胞和血清学变化，并诱导实验性哮喘。结果显示，与MS和对照组相比，HA大鼠的探索行为显著增加，焦虑减少。在没有进一步的行为或免疫学挑战的情况下，HA动物表现出增加的离体NK细胞细胞毒性，但没有其他明显的免疫学差异。相比之下，诱导哮喘后，MS动物在白细胞亚群组成中表现出促炎症作用，包括嗜酸性粒细胞数量增加，而与HA相比，IgE和过敏特异性细胞因子IL-13的水平降低。与攻毒前和攻毒后的血浆水平相比，HA动物中促肾上腺皮质激素的增加最为显著。这些数据首次表明，出生后早期的刺激或不良经历在成年期产生了“神经内分泌免疫”界面的长期变化，导致过敏性气道疾病的保护或加重机制。因此，除了遗传和卫生因素，非遗传获得的个体差异有助于哮喘的病理生物学。
Genetic and hygienic factors influence susceptibility to asthma. In autoimmune and inflammatory diseases, additional effects of the psychosocial environment have been demonstrated that might also play a role in asthma. In this study, the impact of different early postnatal stressors on an OVA-induced model of asthma was tested in adulthood. Fischer 344 rats were subjected to either repeated handling stimulation (HA), maternal separation (MS), or were left undisturbed in their first 4 wk of life. Behavioral differences were characterized at the age of 4 mo. At 5 mo of age, immunological cellular and serologic changes were investigated and experimental asthma was induced. Results show significantly increased exploratory behavior and reduced anxiety in HA rats compared with MS and controls. Without further behavioral or immunological challenges, HA animals exhibited an increased ex vivo NK cell cytotoxicity but no other obvious immunological differences. After induction of asthma, in contrast, MS animals exhibited proinflammatory effects in leukocyte subset composition including increased eosinophil numbers, whereas levels of IgE and the allergy-specific cytokine IL-13 were reduced compared with HA. There was a most remarkable increase of adrenocorticotropin in HA animals, comparing pre- to postchallenge plasma levels. These data demonstrate for the first time that early postnatal stimulative or adverse experiences exert long-lasting changes of the "neuroendocrinoimmune" interface in adulthood, resulting in either protective or aggravating mechanisms in allergic airway disease. Thus, in addition to genetic and hygienic factors, nongenetically acquired individual differences contribute to the pathobiology of asthma.