Neuroendocrine modulation of chronic relapsing experimental autoimmune encephalomyelitis: a critical role for the hypothalamic-pituitary-adrenal axis.
Murine relapsing EAE can be profoundly suppressed by restraint stress (RST) administered beginning prior to neuroantigen immunization. This study determined what hormone pathway(s) mediate disease suppression. Our results showed that nadolol (NAD), a beta2-adrenergic antagonist, did not reverse the RST-induced suppression of EAE. However, administration of either RU486 or aminoglutethimide, which block the action of peripheral glucocorticoids, resulted in a partial reversal of EAE suppression. Administration of exogenous corticosterone mimicked the effects of RST, in terms of suppression of EAE, decrease in lymphoid cell numbers and decrease in Thl cytokine production. Therefore, the HPA axis plays a more profound role in the RST-induced suppression of EAE than does the sympathetic nervous system.
Dowdell
K C
KC
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine and Public Health, Columbus 43210-1239, USA.
Gienapp
I E
IE
Stuckman
S
S
Wardrop
R M
RM
Whitacre
C C
CC
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004837:Epinephrine / Q000097:blood; D006727:Hormone Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D009248:Nadolol / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D010913:Pituitary-Adrenal System / Q000276:immunology*; D012008:Recurrence; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D000893:Anti-Inflammatory Agents; D006727:Hormone Antagonists; D007376:Interleukin-2; D000616:Aminoglutethimide; D015735:Mifepristone; D009248:Nadolol; D007371:Interferon-gamma; D003345:Corticosterone; D009638:Norepinephrine; D004837:Epinephrine