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.

Female temperament, tumor development and life span: Relation to glucocorticoid and tumor necrosis factor α levels in rats

“…Most likely, glucocorticoid-independent mechanisms of thymic atrophy (Krenger et al, 2000) are related to catecholamine action (see Madden, 2003 for a comprehensive review of catecholamine effects on immune function). The effects of catecholamines on thymus weight and lifespan may be mediated by glucocorticoids in that NE production can stimulate interleukin-1 in turn stimulating the HPA axis (Shintani et al, 1995). Further work will have to include measures of personality-linked variance in catecholamines to better understand mechanisms underlying a relationship between personality, immune function and cancer susceptibility/progression (Elenkov & Chrousos, 1999).…”

Changes in Monoamine Turnover in the Brain of Cachectic Mice Bearing Colon‐26 Tumor Cells

“…Dunn (1993) revealed that intraperitoneal injection of IL-1/3 into mice accelerated NA turnover in cerebral cortex, hypothalamus, and brainstem and 5-HT turnover in cerebral cortex and brainstem. Shintani et al (1995) reported that immobilization stress in rats induced elevation of steady-state levels of hypothalamic NA, DA, and 5-HT through the enhanced production of IL-1~3in the brain. Although the effect of IL-1,@ on NAergic and serotonergic neurons observed in rats is consistent with the change in cachectic mice in the present study, the decrease in DAergic neuron activity in cachectic mice could not be induced by IL-1/3 (Dunn, 1993;Shintani et al, 1995).…”

“…Shintani et al (1995) reported that immobilization stress in rats induced elevation of steady-state levels of hypothalamic NA, DA, and 5-HT through the enhanced production of IL-1~3in the brain. Although the effect of IL-1,@ on NAergic and serotonergic neurons observed in rats is consistent with the change in cachectic mice in the present study, the decrease in DAergic neuron activity in cachectic mice could not be induced by IL-1/3 (Dunn, 1993;Shintani et al, 1995). Furthermore, Zalcman et al (1994) reported that intraperitoneal injection of IL-6 into mice accelerated DA and S-HT activities.…”

Serotonin depletion does not alter lipopolysaccharide-induced activation of the rat paraventricular nucleus

“…In addition to elevating serotonin levels, intrahippocampal IL-1 also increases HPA axis activity as evidenced by increases in plasma ACTH and corticosterone levels (Linthorst et al 1994). Immobilization stress elevates plasma ACTH and monoamines including serotonin within the hypothalamus, an effect which can be blocked by the use of an IL-1 receptor antagonist (Shintani et al 1995). Hence evidence exists suggesting that serotonin could play a role in mediating the effects of IL-1 , or LPS on the HPA axis.…”