Study sheds light on pathway from stress to inflammation
MedWire News: US-Canadian researchers have developed and tested a model to illustrate a hypothetical pathway by which chronic stress can lead, via glucocorticoid receptor resistance (GCR), to systemic 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," remark Sheldon Cohen (Carnegie Mellon University, Pittsburgh, Pennsylvania) and co-authors in the Proceedings of the National Academy of Sciences.
Cohen et al's model proposes that chronic stress leads to GCR, a condition characterized by reduced sensitivity of the immune cells that normally terminate the inflammatory response.
Without sufficient glucocorticoid regulation, the duration and/or intensity of the inflammatory response increases, heightening the risk for exacerbations of acute disease (such as asthma and autoimmune conditions) as well as for the onset and progression of chronic inflammation diseases (such as cardiovascular disease and Type 2 diabetes).
To test their model, Cohen's team performed two "viral-challenge" studies. First, they enrolled 276 healthy adult volunteers, exposed them to one of two rhinoviruses, and monitored them for 5 days for signs and symptoms of the common cold.
After controlling for confounding variables, volunteers who reported recently experiencing a major stressful life event had an increased risk for developing a cold following virus exposure, at an odds ratio of 1.99 versus nonstressed individuals.
In the second experiment, 79 individuals were exposed to a rhinovirus and then their nasal secretions were monitored for 5 days for levels of proinflammatory cytokines. In this cohort, GCR levels at baseline were significantly and positively correlated with subsequent cytokine production.
Based on their results, Cohen et al propose that exposure to a major stressful life event can result in GCR, which, in turn, would interfere with hypothalamic-pituitary-adrenocortical axis downregulation of local proinflammatory cytokine response to an infectious agent.
"Without appropriate cortisol regulation of the local cytokine response, there would be an exaggerated expression of the signs of upper respiratory infections, which are generated by the proinflammatory response," they remark.
They add: "Future research on GCR would benefit from quantification of GR subtypes, whose relative abundance might underlie the findings observed here."
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By Joanna Lyford