The comparison of changes in behavior, neurochemistry, endocrine, and immune functions after different routes, doses and durations of administrations of IL-1beta in rats.
The comparison of changes in behavior, neurochemistry, endocrine, and immune functions after different routes, doses and durations of administrations of IL-1beta in rats.
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DOI：
10.1055/s-2006-941557
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发表时间：
2006-05
影响因子：
4.3
通讯作者：
C. Song;Horrobin Df;Leonard Be
中科院分区：
文献类型：
--
作者：
C. Song;Horrobin Df;Leonard Be
背景 大脑和外周中白细胞介素-1β (IL-1) 的增加与神经退行性疾病和精神疾病有关。然而，不同IL-1来源、给药途径、剂量和治疗持续时间的结果不一致且混乱。 IL-1 诱导的行为改变发生的神经内分泌免疫机制仍不清楚。方法在本研究中，研究了大鼠腹膜内（ip）或脑室内（icv）注射重组IL-1对行为、皮质酮分泌、外周炎症反应和脑单胺的急性和亚慢性影响。结果 在旷场装置中，IL-1 (ip) 增加了运动活性，但在 icv 给药后降低了运动活性。与腹腔注射给药相比，ICV后IL-1在高架十字迷宫中具有更大的致焦虑作用。在莫里斯水迷宫中，空间记忆仅在亚慢性和静脉注射后受损。急性和亚慢性 IL-1 都会增加血清皮质酮浓度，并减少全血培养物中抗炎细胞因子 IL-10 的释放。然而，中枢给药的IL-1增加了血培养物中PGE2的释放，而外周给药则减少了PGE2的释放。亚慢性给药后，几个边缘区域的去甲肾上腺素浓度降低，而血清素和多巴胺的周转率增加。讨论 这些结果表明：1) IL-1 的作用取决于给药剂量、途径和持续时间，2) IL-1 增强大鼠对应激环境刺激的反应能力。此外，亚慢性施用IL-1会引起行为、神经递质、激素和免疫的变化，这些变化可能与抑郁症等一些精神疾病的机制有关。
BACKGROUND Increased interleukin-1beta (IL-1) in the brain and periphery has been associated with neurodegenerative and psychiatric disorders. However, results from different IL-1 sources, administrating routes, doses and treatment duration were inconsistent and confused. The neuroendocrine-immune mechanism by which IL-1-induced behavioral changes occur is still unclear. METHODS In the present study, the acute and sub-chronic effects of rat recombinant IL-1, following either intraperitoneal (ip) or intracerebroventricular (icv) injection, were studied on the behavior, corticosterone secretion, peripheral inflammatory responses and brain monoamines. RESULTS In the open field apparatus, IL-1 (ip) increased locomotor activity but decreased the activity following icv administration. IL-1 had a greater anxiogenic effect in the elevated plus maze after icv than after ip administration. In the Morris water maze spatial memory was only impaired following sub-chronic and icv administration. Both acute and sub-chronic IL-1 increased the serum corticosterone concentration and decreased the release of the anti-inflammatory cytokine IL-10 from whole blood cultures. However, centrally administered IL-1 increased, while peripherally administered decreased, the release of PGE2 from blood cultures. After sub-chronic administration, the noradrenaline concentration was decreased in several limbic regions, while the turnovers of serotonin and dopamine were increased. DISCUSSION These results suggest that 1) IL-1 effects depended on the dose, route and duration of administration, and 2) IL-1 enhances the responsiveness of rats to stressful environmental stimuli. In addition, the sub-chronic administration of IL-1 induces behavioral, neurotransmitter, hormonal and immune changes that may be causally implicated in the mechanism of some of psychiatric disorders such as depression.