Susceptibility and resistance to experimental allergic encephalomyelitis: Relationship with hypothalamic-pituitary-adrenocortical axis responsivenessin the rat

Susceptibility to experimental allergic encephalomyelitis (EAE) may be infl uenced by variations in the production of endogenous glucocorticoids. We in vestigated whether this concept is consistent across different genotypes an d paradigms of EAE. In the major histocompatibility complex-disparate rat s trains, 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, respect ively. We analyzed hormone production in EAE and after exposure to novel en vironment. DA and BN rats showed a robust hypothalamic-pituitary-adrenocort ical (HPA) axis response to novelty stress and produced significantly highe r ACTH and corticosterone plasma levels compared with LEW rats. However, HP A axis responsiveness was not associated with a generalized resistance to E AE, as both DA and LEW rats were susceptible to myelin basic protein-induce d EAE. Moreover, both robust HPA responder strains, DA and the EAE-resistan t BN rat, were highly susceptible to myelin oligodendrocyte glycoprotein-in duced 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 axi s characteristics are not a predictor of disease susceptibility in EAE.