RT Journal Article
SR Electronic
T1 Involvement of interleukin-1 in immobilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1961
OP 1970
DO 10.1523/JNEUROSCI.15-03-01961.1995
VO 15
IS 3
A1 F Shintani
A1 T Nakaki
A1 S Kanba
A1 K Sato
A1 G Yagi
A1 M Shiozawa
A1 S Aiso
A1 R Kato
A1 M Asai
YR 1995
UL http://www.jneurosci.org/content/15/3/1961.abstract
AB 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.