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Clinical Trial
. 2012 Apr 17;109(16):5995-9.
doi: 10.1073/pnas.1118355109. Epub 2012 Apr 2.

Chronic Stress, Glucocorticoid Receptor Resistance, Inflammation, and Disease Risk

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Free PMC article
Clinical Trial

Chronic Stress, Glucocorticoid Receptor Resistance, Inflammation, and Disease Risk

Sheldon Cohen et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

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.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Association between plasma cortisol and the ratio of neutrophils to lymphocytes for subjects experiencing and not experiencing a significant stressful life event during the last year. Lack of correlation is a marker of GCR. Filled circles/solid line, major stressful life event; open circles/dashed line, no stressful event.
Fig. 2.
Fig. 2.
Association between plasma cortisol and the ratio of neutrophils to lymphocytes for subjects who developed and did not develop a cold after exposure to a rhinovirus. Lack of correlation is a marker of GCR. Filled circles/solid line, meets cold criterion; open circles/dashed line, does not meet cold criterion.

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