The effects of the anti-glucocorticoid RU 38486 on steroid-mediated suppression of experimental allergic encephalomyelitis (EAE) in the Lewis rat.
Lewis rats, sensitised for the autoimmune condition EAE received a range of doses of the steroid dexamethasone at various times post-inoculation in an attempt to modify the clinical course of the disease. Depending upon the dosing regime employed microgram quantities of the steroid were sufficient to significantly inhibit the clinical development of EAE and milligram doses of the drug completely suppressed the emergence of disease. Administration of the potent anti-glucocorticoid RU38486 to sensitised animals intensified the clinical course of EAE and reversed the steroid-induced inhibition of the disease. Furthermore, after the characteristic loss of neurological symptoms in rats receiving dexamethasone and RU38486, readministration of the anti-glucocorticoid resulted in clinical relapses in the majority of animals. The study emphasises the potent effects of exogenous, physiologically relevant doses of steroid on the course of EAE and, as a result of the observations made using RU38486, considers the role of endogenous steroids in the control of the disease in the rat.
Bolton
C
C
Pharmacology Group, University of Bath, U.K.
Flower
R J
RJ
D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D003907:Dexamethasone / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D004963:Estrenes / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D008297:Male; D015735:Mifepristone; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence
D004963:Estrenes; D005938:Glucocorticoids; D015735:Mifepristone; D003907:Dexamethasone