Endogenous corticosteroids modulate lymphoproliferation and susceptibility to experimental allergic encephalomyelitis in the Brown Norway rat.
Successful induction of the experimental autoimmune disease allergic encephalomyelitis (EAE) depends, in part, upon species susceptibility. The Lewis rat is highly susceptible to EAE whereas the Brown Norway (BN) strain is resistant to induction. Endogenous glucocorticoids influence the manifestation of the disease and recovery from neurological deficits. Moreover, abrogation of the curative steroid-mediated effects converts the condition to a terminal state. In the present study treatment of EAE-inoculated BN rats with the steroid antagonist RU486 (Mifepristone) failed to influence the resistance to symptoms. Similarly, adrenalectomy (ADX) prior to sensitisation did not allow the development of clinical EAE but did facilitate neuroperivascular accumulation of inflammatory-type cells. However, RU486 treatment after ADX induced neurological and histological signs of EAE in the majority of animals. Lymphocyte proliferation studies on cells isolated from BN rats treated with RU486 revealed an enhanced responsiveness to mitogenic and antigenic stimulation. These results strongly implicate endogenous steroids in the expansion of immune cell numbers which would be an absolute requirement for the expression of autoimmune-based neurological disease in otherwise resistant rats.
Peers
S H
SH
Department of Biochemical Pharmacology, Medical College of St. Bartholomew's Hospital, London, UK.
Duncan
G S
GS
Flower
R J
RJ
Bolton
C
C
D000305:Adrenal Cortex Hormones / Q000037:antagonists & inhibitors / Q000097:blood*; D000315:Adrenalectomy; D000818:Animals; D002455:Cell Division; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology*; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013045:Species Specificity
D000305:Adrenal Cortex Hormones; D015735:Mifepristone