Susceptibility and resistance to experimental allergic encephalomyelitis: relationship with hypothalamic-pituitary-adrenocortical axis responsiveness in the rat.
Susceptibility to experimental allergic encephalomyelitis (EAE) may be influenced by variations in the production of endogenous glucocorticoids. We investigated whether this concept is consistent across different genotypes and paradigms of EAE. In the major histocompatibility complex-disparate rat strains, Lewis (LEW), Brown Norway (BN), and Dark Agouti (DA), inflammatory and inflammatory-demyelinating variants of EAE were induced by immunization with myelin basic protein and myelin oligodendrocyte glycoprotein, respectively. We analyzed hormone production in EAE and after exposure to novel environment. DA and BN rats showed a robust hypothalamic-pituitary-adrenocortical (HPA) axis response to novelty stress and produced significantly higher ACTH and corticosterone plasma levels compared with LEW rats. However, HPA axis responsiveness was not associated with a generalized resistance to EAE, as both DA and LEW rats were susceptible to myelin basic protein-induced EAE. Moreover, both robust HPA responder strains, DA and the EAE-resistant BN rat, were highly susceptible to myelin oligodendrocyte glycoprotein-induced EAE. In animals of all strains, clinical disease was associated with significantly elevated plasma levels of corticosterone, and no differences in brain glucocorticoid-binding receptors were detected. Therefore, HPA axis characteristics are not a predictor of disease susceptibility in EAE.
Stefferl
A
A
Max Planck Institute of Psychiatry, Section of Neuroimmunoendocrinology, Munich, Germany.
Linington
C
C
Holsboer
F
F
Reul
J M
JM
D000302:Adrenal Cortex / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D003345:Corticosterone / Q000097:blood; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006168:Guinea Pigs; D007031:Hypothalamus / Q000503:physiopathology*; D007113:Immunity, Innate; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010902:Pituitary Gland / Q000503:physiopathology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew
D000954:Antigens, Surface; C571328:Mog protein, rat; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone