title: Chronic stimulation of the pituitary-adrenal axis in rats by interleukin-1 beta infusion: in vivo and in vitro studies.
abstract: It has been shown that acute administration of interleukin-1 (IL-1) to rats elicits a transitory increase in plasma ACTH and corticosterone (B) levels. To investigate the effects of chronic administration of IL-1 on plasma ACTH and B levels, in the present study rats were equipped with Alzet osmotic minipumps loaded with either IL-1 (delivery rate 0.5, 2.0, or 4.0 micrograms/24 h, ip, for 1 week) or saline. At the end of the treatment the rats were decapitated, the adrenals were weighed, and the in vitro release of beta-endorphin (beta E) by the anterior pituitary and that of B by the adrenal gland were measured. Continuous administration of 2.0 and 4.0 micrograms IL-1/24 h resulted in a persistent increase in plasma ACTH and B concentrations compared to the levels in saline-infused rats, with peak levels on the first day of administration. In addition, adrenal weights of IL-1 rats were significantly higher than those of saline rats. The 4.0-micrograms IL-1/day in vivo treatment induced an increase in spontaneous in vitro secretion of beta E and B, while the in vitro responses of the pituitary (to CRF) and the adrenal (to ACTH) of animals treated in vivo with IL-1 were significantly diminished. IL-1 at a dose of 0.5 microgram failed to affect plasma ACTH and B values, adrenal weight, and in vitro beta E and B secretion. Chronic infusion of rats with 4.0 micrograms IL-1/day induced prolonged fever, whereas at lower doses of IL-1 (2.0 and 0.5 micrograms), temperatures were elevated only on the first 2 days of infusion. IL-1 at doses of 2.0 and 4.0 micrograms/day induced suppression of body weight gain on the first 2 days of the treatment period compared to saline treatment. Plasma norepinephrine and/or epinephrine concentrations were raised only on day 1 of the 2.0- and 4.0-micrograms IL-1 experiments. Thus, the observed effects of IL-1 on the hypothalamo-pituitary-adrenal axis probably do not result merely from stress induced by the treatment. Taken together, our data show the potential of IL-1 to induce a dose-dependent and long term activation of the pituitary-adrenal axis.
authors.affiliation: Department of Medicine, St. Radboud Hospital, University of Nijmegen, The Netherlands.
authors.forename: C G
authors.initials: CG
authors.lastname: Sweep
authors.forename: M J
authors.initials: MJ
authors.lastname: van der Meer
authors.forename: A R
authors.initials: AR
authors.lastname: Hermus
authors.forename: A G
authors.initials: AG
authors.lastname: Smals
authors.forename: J W
authors.initials: JW
authors.lastname: van der Meer
authors.forename: G J
authors.initials: GJ
authors.lastname: Pesman
authors.forename: S J
authors.initials: SJ
authors.lastname: Willemsen
authors.forename: T J
authors.initials: TJ
authors.lastname: Benraad
authors.forename: P W
authors.initials: PW
authors.lastname: Kloppenborg
mesh_terms: D000311:Adrenal Glands / Q000033:anatomy & histology / Q000737:chemistry / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000032:analysis / Q000097:blood; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D066298:In Vitro Techniques; D007260:Infusion Pumps; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008137:Longitudinal Studies; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000737:chemistry; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002395:Catecholamines; D007375:Interleukin-1; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D003345:Corticosterone