The hypothalamic-pituitary-adrenal axis in the pathogenesis of rheumatic diseases.
Many studies have demonstrated altered HPA axis activity in patients with rheumatic diseases. In the case of autoimmune inflammatory diseases, circumstantial evidence suggests that failure of the neuroendocrine-immune regulatory loop may lead to insufficient production of endogenous glucocorticoid. Nevertheless, in human autoimmune disease, it is not possible to determine if altered HPA axis activity predates the onset of chronic inflammation. Animal studies and some early genetic studies in RA patients lend credibility to the argument that insufficient HPA axis response to inflammatory stimuli may increase susceptibility to, or severity of, these diseases. Most patients with rheumatic diseases complain of musculoskeletal pain. There is evidence of HPA axis involvement in acute and chronic pain. In the case of FM, pain cannot be explained on the basis of inflammation or altered musculoskeletal anatomy. This has led to the hypothesis that central nervous system mechanisms contribute to the symptom of somatic pain. Again, it is unclear if the observed HPA axis abnormalities reflect pre-existing vulnerability to the FM spectrum of disease, or whether chronic somatic symptoms alter HPA axis activity. Availability of technology to study better central components of the HPA axis may shed further light on its role in the pathogenesis of inflammatory autoimmune rheumatic diseases and musculoskeletal pain syndromes.
Crofford
Leslie J
LJ
Department of Internal Medicine and Rheumatology, University of Michigan, Room 5510, MSRB I, 1150 W. Medical Center Dr., An Arbor, MI 48109-0680, USA. crofford@umich.edu
D000311:Adrenal Glands / Q000503:physiopathology*; D000818:Animals; D001172:Arthritis, Rheumatoid; D004195:Disease Models, Animal; D005246:Feedback; D005356:Fibromyalgia; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology*; D007109:Immunity; D008180:Lupus Erythematosus, Systemic; D009490:Neurosecretory Systems / Q000503:physiopathology; D010902:Pituitary Gland / Q000503:physiopathology*; D012216:Rheumatic Diseases / Q000209:etiology* / Q000503:physiopathology