Figure 4: Imbalance of neural, hormonal and immune regulation in autoimmunity. A) The common patterns of neural-Immune dysregulation in autoimmune diseases, including RA, are illustrated. The stress systemcomposed of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic and parasympathetic nervous systems (SNS and PaSNS, respectively) regulate immune responses, promoting immune functions in responses to anger signals and pathogens, and inhibiting immune responses as these threats are removed homeostasis is restored. In autoimmunity, homeostasis is not restored, and an imbalance in these cross-regulatory systems develops. B) Changes in the ability of the autonomic nervous system to appropriately control body functions, such as those listed on the right side of the panel for RA patients, are often observed in patients with autoimmune diseases. These findings indicate ANS dysregulation in these diseases. The observed pattern of dysregulation generally observed for each major regulatory system is indicated by the direction of the arrows. The SNS becomes hyperreactive, whereas the PaSNS becomes hyporeactive. Similarly, dampened responsiveness of glucocorticoid receptors to glucocorticoids in patients with RA and other autoimmune disorders indicates a hypo-functional HPA axis. Increased immune system activation (production of proinflammatory cytokines and auto-antibodies and increased activity of autoreactive T cells) may, in part, result for from lost inhibitory regulation by these neural and neuroendocrine pathways that are required to restore immune system homeostasis.