title: Regulation of chronic relapsing experimental allergic encephalomyelitis by endogenous and exogenous glucocorticoids.
abstract: Expression, development and resolution of the acute form of experimental allergic encephalomyelitis (EAE), typically induced in the highly susceptible Lewis rat, are closely regulated by endogenous corticosteroids. Administration of synthetic glucocorticoids also efficiently controls the manifestation of disease. The pivotal role played by the corticosteroids in modifying the induction and progression of EAE is further emphasised by a reversal of corticoid-mediated effects through adrenalectomy or treatment with the steroid receptor antagonist RU486 (mifepristone). Chronic relapsing EAE (CREAE) is characterised by acute symptoms, periods of remission and re-emergence of disease. The mechanisms governing the development of CREAE are unclear, but may require the regulatory influence of endogenous glucocorticoids. The current study has monitored circulating corticosteroids throughout the course of CREAE in the Biozzi ABH mouse and found that major fluctuations in systemic levels coincide with the relapsing-remitting phases of the disease. Furthermore, increasing circulating adrenocorticoids through administration of the steroidal compound dexamethasone markedly suppresses the occurrence of acute signs. The importance of the glucocorticoids in controlling CREAE is again highlighted by the intensification of symptoms and reduction in the survival rate of inoculated mice receiving RU486 prior to and during the acute phase of disease. The data reinforce the amelioratory actions of exogenous and naturally occurring glucocorticoids in the pathogenesis of EAE and extend earlier observations in the monophasic disease by demonstrating corticosteroid-dependent effects in a relapsing-remitting mouse model.
authors.affiliation: Pharmacology Group, School of Pharmacy and Pharmacology, University of Bath, Claverton Down, UK. c.bolton@bath.ac.uk
authors.forename: C
authors.initials: C
authors.lastname: Bolton
authors.forename: J K
authors.initials: JK
authors.lastname: O'Neill
authors.forename: S J
authors.initials: SJ
authors.lastname: Allen
authors.forename: D
authors.initials: D
authors.lastname: Baker
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006968:Hypersensitivity, Delayed; D008297:Male; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D015213:Neuroimmunomodulation / Q000502:physiology; D051381:Rats; D012008:Recurrence; D013045:Species Specificity
chemical_list: D005938:Glucocorticoids; D006727:Hormone Antagonists; D015735:Mifepristone; D003907:Dexamethasone; D003345:Corticosterone