Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk
Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk
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DOI：
10.1073/pnas.1118355109
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发表时间：
2012-04-17
影响因子：
11.1
通讯作者：
Turner, Ronald B.
中科院分区：
文献类型：
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作者：
Cohen, Sheldon;Janicki-Deverts, Denise;Turner, Ronald B.
我们提出了一个模型，其中慢性应激导致糖皮质激素受体抵抗（GCR），这反过来又导致未能下调炎症反应。在这里，我们在两个病毒攻击研究中测试该模型。在研究1中，我们评估了276名健康成年志愿者的压力生活事件、GCR和对照变量，包括基线抗病毒抗体、年龄、体重指数（BMI）、季节、种族、性别、教育和病毒类型。志愿者随后被隔离，暴露于两种鼻病毒中的一种，并随后用鼻洗液进行5天的病毒分离和评估普通感冒的体征/症状。在研究2中，我们评估了79名随后接触鼻病毒的受试者的相同控制变量和GCR，并在基线和病毒攻击后5天监测局部（鼻分泌物中）促炎细胞因子（IL-1 β、TNF-α和IL-6）的产生。研究1：在对控制变量进行协变后，那些最近暴露于长期威胁性压力经历的人表现出GCR;而那些GCR的人随后患感冒的风险更高。研究2：在研究1中使用相同的对照组，更大的GCR预测感染受试者中产生更多的局部促炎细胞因子。这些数据为一个模型提供了支持，该模型表明长期的应激源导致GCR，这反过来又干扰了炎症的适当调节。由于炎症在多种疾病的发生和发展中起着重要作用，因此该模型可能对理解压力在健康中的作用具有广泛的意义。
We propose a model wherein chronic stress results in glucocorticoid receptor resistance (GCR) that, in turn, results in failure to down-regulate inflammatory response. Here we test the model in two viral-challenge studies. In study 1, we assessed stressful life events, GCR, and control variables including baseline antibody to the challenge virus, age, body mass index (BMI), season, race, sex, education, and virus type in 276 healthy adult volunteers. The volunteers were subsequently quarantined, exposed to one of two rhinoviruses, and followed for 5 d with nasal washes for viral isolation and assessment of signs/symptoms of a common cold. In study 2, we assessed the same control variables and GCR in 79 subjects who were subsequently exposed to a rhinovirus and monitored at baseline and for 5 d after viral challenge for the production of local (in nasal secretions) proinflammatory cytokines (IL-1 beta, TNF-alpha, and IL-6). Study 1: After covarying the control variables, those with recent exposure to a long-term threatening stressful experience demonstrated GCR; and those with GCR were at higher risk of subsequently developing a cold. Study 2: With the same controls used in study 1, greater GCR predicted the production of more local proinflammatory cytokines among infected subjects. These data provide support for a model suggesting that prolonged stressors result in GCR, which, in turn, interferes with appropriate regulation of inflammation. Because inflammation plays an important role in the onset and progression of a wide range of diseases, this model may have broad implications for understanding the role of stress in health.