Chronic Variable Stress May Promote Autoimmunity through Induction of Glucocorticoid Resistance

psychological stress

A new European Journal of Immunology study links chronic stress and autoimmunity through a mechanism referred to as glucocorticoid resistance.

The effect of psychological stress on autoimmunity is extremely complex, at multiple levels, and can be in either direction. Often, stress is related to both induction/exacerbation and amelioration of disease activity.

Stress hormones selectively suppress the T helper (Th)1-related cellular immunity, and potentiate Th2 responses (inducing a Th2 shift), and thus suppress, in general, autoimmune reactions.

Several lines of evidence also indicate that a hyper- or hypo-activity of the stress system, or, alternatively, a dysfunctional hypothalamic–pituitary–adrenal (HPA) axis or sympathetic nervous system are involved in the pathogenesis of autoimmune diseases.

However, the question still remains, in some cases e.g. multiple sclerosis and psoriasis, why chronic stress contributes to the relapse of autoimmune activity.

The study published in the March 2013 issue of the European Journal of Immunology may provide some new insights into this phenomenon.

In this study, Idan Harpaz and colleagues from the Ben-Gurion Universityof the Negev, Beer Sheva, Israel, demonstrate that prolonged stress exposure – 24 days of chronic variable stress (CVS) – exacerbates, rather than ameliorates, experimental autoimmune encephalomyelitis (EAE) in female C57BL/6 mice.

This effect was prevented by blocking corticosterone (CORT) signaling. Of note, during basal, non-stressed conditions, females exhibited substantially higher CORT levels and an attenuated EAE than males. However, in females C57BL/6 mice, CVS induced a significantly worsened EAE and a shift toward proinflammatory Th1/Th17 immune responses and a decreased proportion of CD4+CD25+ Treg cells.

The authors discuss that these observations may indicate that while the HPA axis provides immunosuppression under basal conditions, prolonged exposure to chronic stress may result in an attenuated CORT response to stimuli, and CORT resistance in proinflammatory T-cell lineages.

Through this mechanism, chronic stress may contribute to exacerbations of autoimmune diseases.

According to the authors, their results also suggest that patients suffering from autoimmune diseases may perhaps develop steroid resistance due to persistent glucocorticoids exposure.

Source: Eur J Immunol, 2013, 43:758. doi: 10.1002/eji.201242613. Epub 2013 Jan 31

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