title: Involvement of interleukin-1 in immobilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat.
abstract: We investigated whether interleukin-1 (IL-1) activity in the rat hypothalamus was increased by immobilization stress (IS), and whether pretreatment with an interleukin-1 receptor antagonist (IL-1Ra) is capable of inhibiting IS-induced elevations of hypothalamic norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and the levels of their metabolites as well as of plasma adrenocorticotropic hormone (ACTH). IL-1 activity was estimated with a bioassay using mouse thymocyte proliferation in the presence of concanavalin A. IL-1Ra was administered directly into the anterior hypothalamus, and monoamines were determined using a microdialysis technique and an HPLC system. First, we found that levels of IL-1 activity in the rat hypothalamus reached a maximum at 60 min after starting IS. Second, IL-1Ra (2 micrograms) significantly inhibited IS-induced increases in hypothalamic NE, DA, and 5-HT levels as well as the levels of their metabolites. In addition, IL-1Ra (2 micrograms) also inhibited the IS-induced elevation of plasma ACTH levels. Third, timing effects of IL-1Ra administration on the IS-induced monoamines or ACTH responses were examined. IL-1Ra (2 micrograms) administered at 5 or 60 min before the start of IS, but not at 5 or 60 min after IS had been started, exerted inhibitory effects on these responses, indicating that the effects of IL-1 occurred within 5 min after the initiation of IS. In summary, these results suggest that IS enhances biologically active IL-1 in the hypothalamus, and that hypothalamic IL-1 plays a role in the regulation of IS-induced responses including elevated monoamine release in the hypothalamus and activation of the hypothalamo-pituitary-adrenal axis. Moreover, since 5 min is too short a time for IS to induce production of IL-1, IS may augment the effects of preexisting IL-1 in the hypothalamus.
authors.affiliation: Department of Neuro-psychiatry, Keio University School of Medicine, Tokyo, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Shintani
authors.forename: T
authors.initials: T
authors.lastname: Nakaki
authors.forename: S
authors.initials: S
authors.lastname: Kanba
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: G
authors.initials: G
authors.lastname: Yagi
authors.forename: M
authors.initials: M
authors.lastname: Shiozawa
authors.forename: S
authors.initials: S
authors.lastname: Aiso
authors.forename: R
authors.initials: R
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Asai
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D007103:Immobilization; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012701:Serotonin; D000324:Adrenocorticotropic Hormone; D004298:Dopamine; D009638:Norepinephrine