Role of the cytokines in the neuroendocrine-immune system axis.

A rapidly growing body of evidence reveals that complex networks of communication exist between the neuroendocrine and the immune systems. Essential to the maintenance and function of the immune-endocrine circuitry are an array of chemical mediators produced by cells of the immune and endocrine systems. Cytokines are glycoproteins (molecular masses of 15,000-20,000) that are elaborated by antigen-activated immune cells and responsible for orchestrating immune cellular activities. These inflammatory mediators also affect the functioning of the neuroendocrine system. Thus, interleukin-1 (IL-1), IL-2, IL-4, IL-6, tumor necrosis factor-alpha and interferon-gamma affect the secretion of hypothalamic and anterior pituitary hormones in vitro and in vivo, and specific high-affinity receptors for IL-1, IL-2, and IL-6 have been identified in neuroendocrine tissues. A paracrine role for these factors in the regulation of neuroendocrine function may be advanced because certain of these mediators (e.g., IL-1, IL-6) are present in the hypothalamus as well as the anterior and neurointermediate lobes of the pituitary. The production of these cytokines in neuroendocrine cells is enhanced by neuropeptides, endotoxin, and other cytokines. We propose that the local neuroendocrine cytokinergic tone may act in a facilitative manner to enhance the secretion of hypothalamic-pituitary hormones.