Neuroendocrine-immune system interactions The immune-hypothalamo-pituitary-adrenal axis.

Bidirectional interactions between the immune system and the hypothalamo-pituitary-adrenal (HPA) axis may represent an important mechanism that prevents overexuberant immune responses. In this network, cytokines play an important role in modulating the HPA axis response at all three levels: the hypothalamus, the pituitary gland, and the adrenals. Acute effects of cytokines are produced at the hypothalamic level by altered release of hypophysiotropic hormones, whereas pituitary and adrenal actions are slower but probably more important in response to prolonged release of cytokines, as it occurs in infection or inflammation. Further studies are needed to determine the precise mechanism through which circulating cytokines affect the HPA axis function within the central nervous system and to evaluate the relevance of these interactions in physiologic and pathophysiologic situations in humans.