The Stress System And The Hypothalamic–Pituitary–Adrenal Axis In Rheumatoid Arthritis

Abstract The neuroendocrine and immune systems communicate with each other via a number of shared regulatory mediators (steroid hormones, neuropeptides, and cytokines) and receptors, and play major roles in maintenance of homeostasis and adaptation . Exposure to inflammatory stimuli is followed by an integrated response from the site of inflammation via the release of specific cytokines, the key ones being interleukin (IL) IL-1, tumor necrosis factor-alpha (TNF-), and IL-6, and via activation of neural afferent autonomic sensory fibers. These cytokines and afferent nerves lead to the secretion of acute phase proteins by the liver, and initiate a non-specific response via the stimulation of the hypothalamic-pituitary-adrenal (HPA) axis and the systemic/ adrenomedullary sympathetic nervous systems (SNS) . This leads to systemic elevations of glucocorticoids and catecholamines (Cas), which aim at regulating the inflammation at the site of initiation . Rheumatoid arthritis (RA) is a paradigmatic, multifactorial autoimmune disease that is derived from the patient’s excessiveimmune and inflammatory response . In this chapter, the current understanding of interactions of the stress and immune systems and their physiologic and pathophysiologic implications in the initiation/perpetuation of the inflammatory component in RA will be discussed. The use of potential therapeutic means based on the presence of such alterations will also be raised.