Feed-back interactions between immunological cells and the hypothalamus-pituitary-adrenal axis

There is now increasing evidence that complex networks of interactions between immunological cells and endocrine, autonomic and brain structures operate during physiological and pathological conditions. Such interactions imply the existence of afferent messengers derived from the immune system, such as lymphokines and monokines, capable of integrating immune-neuroendocrine circuits. The operation of a glucocorticoid-associated immunoregulatory circuit is discussed as an example of these interactions. Under basal conditions, in non-overtly immunized animals, endogenous levels of glucocorticoids affect the number of immunoglobulin-secreting cells. At the time of the peak of the immune response to innocuous antigens, as well as following inoculation of infective agents, endotoxins or tumour cells, immunological cells release cytokines which can stimulate the pituitary-adrenal axis. The acute effect of these cytokines is mediated by stimulation of the release of corticotropin-releasing factor from the hypothalamus. Thus, immunological cells are not only influenced by glucocorticoids but their products can also control the activity of the hypothalamus-pituitary-adrenal axis. The possible relevance of these findings for immunoregulation and their implications for pathology are discussed.