Grant: Operating Grant

It is now well accepted that the occurrence of the immune activation must be conveyed to the brain to allow coordination of the appropriate metabolic, behavioral, and endocrine changes necessary for the restoration of the homeostasis. In this concept, the hypothalamus, an area of the brain containing many of the peptides that modulate the neuroendocrine functions, is considered central to the bilateral functional communication pathways between the immune and neuroendocrine axes. The demonstration that cytokines, especially interleukin-1 (IL-1), tumor necrosis factor (TNF) and IL-6, can stimulate neuroendocrine corticotropin-releasing factor (CRF) neurons and the finding that subsequent activation of adrenal steroid release can convey feedback signals to immune cells, is a clear example of the bilateral communication linking the immune and the neuroendocrine systems. Stimulation of the hypothalamic-pituitary adrenal (HPA) axis has been the subject of a great deal of interest because of its major impact on the regulation of the immune response. Glucocorticoids have long been recognized as being among of the most powerful anti-inflammatory agents known, and their use in restraining excessive immune responses has been common in clinical practice since more than 50 years. Inappropriate plasma levels of glucocorticoids may therefore play a crucial role as contributing to deviant regulation of the immune response, indicating the importance to identify and characterize the mechanisms through which local inflammatory process interact with the neuroendocrine system.