Effect of chronic stress and in vivo cortisol measures on immune cell glucocorticoid receptor expression and cellular immune activation

Abstract

Chronic psychological stress increases inflammation, providing a mechanism for the elevated risk of infectious, autoimmune and cardiovascular diseases in chronically stressed persons. While the HPA axis plays an important role in mediating the link between stressful events and inflammatory processes, it is becoming increasingly clear that immune cells can become resistant to cortisol, resulting in diminished regulation of inflammation. One potential mechanism of cortisol resistance results from decreased glucocorticoid receptor (GR) expression in immune cells during elevated cortisol exposure. Chronic stress results in chronic high cortisol exposure leading to decreased immune cell GR expression that in turn is associated with greater immune activation. Using flow cytometry we measured immune activation and GR expression (geometric mean fluorescence intensity [gMFI]) in 10 immune cell subsets in 25 post-menopausal females (10 caregivers [CGs] and 15 controls [CNTLs]). Mann–Whitney and Pearson correlations were employed for statistical analysis with p<0.05 considered significant.No statistically significant difference in daily cortisol exposure was observed between CGs and CNTLs; however, CGs did exhibit greater T cell immune activation (p = 0.029). Contrary to our hypothesis, T cell immune activation was not associated with decreased GR expression. In fact, CGs had equal or a trend toward greater GR expression compared to CNTLs. CGs did demonstrate a statistically significant negative correlation between total daily in vivo cortisol levels and GR expression in CD4+ and CD8+ T cells (−0.74 (p<0.02) and −0.81 (p<0.02), respectively). Combining groups, we observed a positive trend in GR expression and perceived stress in two monocyte subsets (CD14br and CD14dimCD16+). A statistically significant negative correlation between GR expression in the pro-inflammatory CD14brCD16+ and CD14dimCD16+ monocyte subsets and their relative frequency was also observed (−0.47 (p=0.02) and −0.52 (p=0.01), respectively).Elevated inflammation during chronic stress may not result simply from down-regulation of GR in immune cells. Cortisol and GR expression may influence the frequencies of pro-inflammatory monocyte subsets (CD14brCD16+ and CD14dimCD16+) that may be important in regulating chronic inflammation.

Keywords

• chronic stress
• glucocorticoid receptor
• inflammation
• cortisol
• immune activation
• flow cytometry
• HPA axis