Neuroendocrine-immune interactions in rheumatoid arthritis: mechanisms of glucocorticoid resistance.
Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial membrane, leading to joint destruction. Many autoimmune diseases and disease states of chronic inflammation are accompanied by alterations in the complex interactions between the endocrine, nervous and immune systems. Glucocorticoids, an end product of the hypothalamic-pituitary-adrenal axis, are a mainstay treatment for many autoimmune diseases, including RA, because of their potent anti-inflammatory action. However, about 30% of patients with RA fail to respond to steroid therapy. There are various mechanisms that may contribute to the development of glucocorticoid resistance in inflammatory disorders, which will be the subject of this review. In addition, glucocorticoid resistance may be a contributing factor in the development of inflammatory/autoimmune diseases themselves. Therefore, further elucidation of these mechanisms will reveal new targets for therapeutic intervention in the treatment of RA.
Silverman
Marni N
MN
Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, National Institutes of Health, Rockville, MD 20852, USA.
Sternberg
Esther M
EM
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004351:Drug Resistance / Q000502:physiology*; D005938:Glucocorticoids / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology / Q000503:physiopathology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D015213:Neuroimmunomodulation / Q000187:drug effects* / Q000276:immunology; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000276:immunology / Q000503:physiopathology
D005938:Glucocorticoids; D007166:Immunosuppressive Agents