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Current Drug Targets - Inflammation & Allergy


ISSN (Print): 1568-010X
ISSN (Online): 1568-010X

Potential Use of Drugs that Target Neural-Immune Pathways in the Treatment of Rheumatoid Arthritis and Other Autoimmune Diseases

Author(s): D. Lorton, C. Lubahn and D. L. Bellinger

Volume 2 , Issue 1 , 2003

Page: [1 - 30] Pages: 30

DOI: 10.2174/1568010033344499

Price: $65


Many autoimmune disorders share two common features, dysregulation of the immune system and stress pathways. Two stress pathways, the hypothalamic-pituitaryadrenal (HPA) axis and the sympathetic nervous system (SNS), regulate immune system responses, through release of corticosteroids and norepinephrine (NE), respectively. These neuromediators act on immune cells via specific receptors on their surface to modulate the production of key regulatory cytokines. Glucocorticoids modulate immune responses by glucocorticoid binding to cytoplasmic glucocorticoid receptors within target cells. NE regulates immune responses through interaction with plasma membrane ß- or α-adrenergic receptors (AR). Both NE and glucocorticoids promote humoral immunity by altering macrophages and T cell cytokine production after an antigen challenge. Glucocorticoids and NE do this by inhibiting interleukin (IL)-12, and interferon (IFN)-γ, which drives cell-mediated immunity. Additionally, catecholamines drive humoral immunity by stimulating macrophage IL-10 production. These catecholamine effects are mediated largely via ß2-AR activation. Both glucocorticoids and NE inhibit inflammation. However, under some circumstances NE promotes inflammation through interaction with macrophage α1-AR and subsequent increases in tumor necrosis factor α (TNFα) production. Although macrophages do not normally express α1-AR, expression of this receptor on macrophages and monocytes occurs in some disease states, including rheumatoid arthritis (RA). Through these mechanisms the HPA axis and the SNS influence the course and progression of RA. Thus, the HPA axis and the SNS are likely to play key roles in the pathology of RA. Furthermore, therapeutic agents targeting the neural pathways that normally regulate immune system homeostasis may prove beneficial for treating RA and other autoimmune diseases.

Keywords: Neural-Immune, sympathetic nervous system (SNS), Glucocorticoids

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