Stress and hypothalamic-pituitary-adrenal axis function in experimental autoimmune encephalomyelitis and multiple sclerosis - a review.
Multiple sclerosis (MS) is an inflammatory and degenerative disease of the CNS with an assumed autoimmune-mediated pathogenesis. Stressful life events have been hypothesized as potential triggers of disease exacerbation. Animal studies using experimental autoimmune encephalomyelitis (EAE), as a model for MS, suggest that decreased hypothalamic-pituitary-adrenal (HPA) function may play a role in the increased susceptibility and severity of the disease. Histopathological studies of the hypothalamus point to disturbances in corticotropin-releasing hormone (CRH) regulation as a result of MS lesions in this area. Functional endocrine tests (e.g., the combined Dexamethasone-CRH test) showed a disturbed negative feedback after steroid application in MS patients. Hyper- and hypoactivity of the HPA axis, have been described to be associated with more severe courses. This paper presents an overview of the evidence for a role of HPA dysfunction in EAE and MS based on stress-experimental studies.
Heesen
C
C
Institute of Neuroimmunology and Clinical MS Research (INiMS), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. heesen@uke.uni-hamburg.de
Gold
S M
SM
Huitinga
I
I
Reul
J M H M
JM
D000818:Animals; D001522:Behavior, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology*; D047109:Fetal Development / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D009103:Multiple Sclerosis / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology*; D013997:Time Factors
D005938:Glucocorticoids