Involvement of interleukin-1 in immobilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat

F. Shintani, T. Nakaki, S. Kanba, K. Sato, G. Yagi, M. Shiozawa, Sadakazu Aiso, R. Kato, M. Asai

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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 starling IS. Second, IL-1Ra (2 μg) significantly inhibited IS-induced increases in hypothalamic NE, DA, and 5-HT levels as well as the levels of their metabolites. In addition, IL-1 Ra (2 μg) also inhibited the IS-induced elevation of plasma ACTH levels. Third, timing effects of IL-1 Ra administration on the IS-induced monoamines or ACTH responses were examined. IL-1Ra (2 μg) 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.

Original languageEnglish
Pages (from-to)1961-1970
Number of pages10
JournalJournal of Neuroscience
Issue number3 I
Publication statusPublished - 1995 Jan 1
Externally publishedYes



  • 5- HT
  • adrenocorticotropic hormone
  • dopamine
  • hypothalamo-pituitary-adrenal axis
  • immobilization stress
  • interleukin- 1
  • interleukin-1 receptor antagonist
  • norepinephrine
  • rat anterior hypothalamus

ASJC Scopus subject areas

  • Neuroscience(all)

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