PNAS：长期压力可能影响身体的炎症应答

近日，来自国际杂志PNAS上的一项研究报告“Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk，”，表示，长期心理压力可能削弱人体调控炎症的能力，该研究可能有助于解释为什么压力常常与许多心理和生理健康问题有关。

Sheldon Cohen及其同事们评估了276位健康的男性和女性的压力水平，把压力定义为和健康无关的生活经历，这一经历对个人施加了适度的和长期的负担。让这些受试者接触到感冒病毒，然后把他们隔离起来。血液测试和对疾病的其他评估表明暴露在长期压力下的受试者的免疫细胞和其他健康人相比对通常能终结身体的炎症应答的激素的敏感度更低。

对82位健康成年人的随访研究表明免疫敏感度减少的被感染者比其他被感染者产生了更高水平的一种能促进炎症的化学信使。这组作者说，这些发现提示长期压力影响炎症的调控，这可能影响到一大批疾病的发作和发展。

doi:10.1073/pnas.1118355109
Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk

Sheldon Cohena,1, Denise Janicki-Devertsa, William J. Doyleb, Gregory E. Millerc, Ellen Frankd, Bruce S. Rabine, and Ronald B. Turnerf

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-1β, TNF-α, 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.