Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection

Compelling data has been amassed indicating that soluble factors, or cytokines, emanating from the immune system can have profound effects on the neuroendocrine system, in particular the hypothalamic-pituitary-adrenal (HPA) axis. HPA activation by cytokines (via the release of glucocorticoids), in turn, has been found to play a critical role in restraining and shaping immune responses. Thus, cytokine-HPA interactions represent a fundamental consideration regarding the maintenance of homeostasis and the development of disease during viral infection. Although reviews exist that focus on the bi-directional communication between the immune system and the HPA axis during viral infection (188,235), others have focused on the immunomodulatory effects of glucocorticoids during viral infection (14,225). This review, however, concentrates on the other side of the bi-directional loop of neuroendocrine-immune interactions, namely, the characterization of HPA axis activity during viral infection and the mechanisms employed by cytokines to stimulate glucocorticoid release.