Shanks N, Windle R J, Perks P A, Harbuz M S, Jessop D S, Ingram C D, Lightman S L
Division of Medicine, University of Bristol, Bristol Royal Infirmary Labs, Marlborough Street, Bristol, BS2 8HW, United Kingdom.
Proc Natl Acad Sci U S A. 2000 May 9;97(10):5645-50. doi: 10.1073/pnas.090571897.
We have investigated whether exposure to Gram-negative bacterial endotoxin in early neonatal life can alter neuroendocrine and immune regulation in adult animals. Exposure of neonatal rats to a low dose of endotoxin resulted in long-term changes in hypothalamic-pituitary-adrenal (HPA) axis activity, with elevated mean plasma corticosterone concentrations that resulted from increased corticosterone pulse frequency and pulse amplitude. In addition to this marked effect on the development of the HPA axis, neonatal endotoxin exposure had long-lasting effects on immune regulation, including increased sensitivity of lymphocytes to stress-induced suppression of proliferation and a remarkable protection from adjuvant-induced arthritis. These findings demonstrate a potent and long-term effect of neonatal exposure to inflammatory stimuli that can program major changes in the development of both neuroendocrine and immunological regulatory mechanisms.
我们研究了新生早期接触革兰氏阴性细菌内毒素是否会改变成年动物的神经内分泌和免疫调节。新生大鼠接触低剂量内毒素会导致下丘脑-垂体-肾上腺（HPA）轴活动的长期变化，血浆皮质酮平均浓度升高，这是由于皮质酮脉冲频率和脉冲幅度增加所致。除了对HPA轴发育有显著影响外，新生期接触内毒素对免疫调节也有持久影响，包括淋巴细胞对应激诱导的增殖抑制敏感性增加以及对佐剂诱导的关节炎有显著保护作用。这些发现表明，新生期接触炎症刺激具有强大而长期的影响，可对神经内分泌和免疫调节机制的发育产生重大改变。
