Figure 1. Role of Glucocorticoids and the Glucocorticoid Receptor in Mediating Feedback Inhibition on IL-1 and CRH: Potential Influence of Cytokines and Antidepressants.
Stressors and immune activation secondary to inflammation and/or infection serve as potent stimuli to corticotropin releasing factor (CRH) and interleukin (IL)-l respectively. Overexpression of these factors in turn can lead to behavioral disorders whose symptoms overlap and fall under the rubric of major depression. Glucocorticoids via their receptors mediate feedback inhibition on CRH and IL-1 release, thus providing a brake on excessively exuberant responses. The relative functioning of the glucocorticoid receptor (GR), therefore serves as a critical determinant of sensitivity to feedback signals. Proinflammatory cytokines have been shown to inhibit GR function, and antidepressants have been shown to enhance GR function. Thus both of these factors serve to change relevant setpoints regarding glucocorticoid sensitivity as well as sensitivity to major depression via the pathways of stress and immune activation.
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