NR3C1 and major depressive disorder: Thus, glucocorticoids and pro-inflammatory cytokines interact closely: increased production of pro-inflammatory cytokines and/or cortisol in the blood can both directly cause depression, and can also cause hyperactivation of the HPA axis, increase the resistance of glucocorticoid receptors, increase cortisol levels and cause the pro-inflammatory status of the immune system, forming a pathological vicious circle.