Phasic hyperactivity of the HPA axis resulting from chronic central IL-2 administration.
Intracerebroventricular infusion of interleukin-2 (IL-2, 15 U h-1 for 14 days) chronically activated the hypothalamic-pituitary-adrenocortical (HPA) axis in rats. IL-2 induced increases in plasma levels of adrenocorticotropic hormone (ACTH, up to two-fold) and corticosterone (up to four-fold) compared with controls. Continuously elevated brain levels of IL-2 did not lead to a persistent HPA activation, but resulted in (two) periods of hormonal hypersecretion. ACTH and corticosterone levels were elevated between days 3 and 5, with changes in corticosterone preceding those of ACTH. Concentrations of corticosterone, but not of ACTH, increased again on day 11. Underscoring its importance as a neuroendocrine regulator, this study reveals that, in addition to its immediate effects, IL-2 induces a complex pattern of chronic HPA stimulation. These findings may functionally relate to several CNS disorders and certain endocrine dysfunctions observed during IL-2 immunotherapy.
Hanisch
U K
UK
Max Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany.
Rowe
W
W
van Rossum
D
D
Meaney
M J
MJ
Quirion
R
R
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D006651:Histocytochemistry; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D007376:Interleukin-2; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone