Song C, Horrobin D F, Leonard B E
Department of Biomedical Science, AVC, University of Prince Edward Island, Charlottetown, Canada.
Pharmacopsychiatry. 2006 May;39(3):88-99. doi: 10.1055/s-2006-941557.
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.
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.
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.
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.
大脑和外周白细胞介素-1β（IL-1）水平升高与神经退行性疾病和精神疾病有关。然而，来自不同IL-1来源、给药途径、剂量和治疗持续时间的结果并不一致且令人困惑。IL-1诱导行为变化的神经内分泌-免疫机制仍不清楚。
在本研究中，研究了大鼠重组IL-1腹腔内（ip）或脑室内（icv）注射后的急性和亚慢性作用，包括对行为、皮质酮分泌、外周炎症反应和脑单胺的影响。
在旷场实验中，腹腔注射IL-1增加运动活动，但脑室内给药后运动活动减少。脑室内注射IL-1后在高架十字迷宫中产生的焦虑效应比腹腔注射后更大。在莫里斯水迷宫中，仅亚慢性脑室内给药后空间记忆受损。急性和亚慢性IL-1均增加血清皮质酮浓度，并降低全血培养物中抗炎细胞因子IL-10的释放。然而，脑内给药的IL-1增加，而外周给药的IL-1降低血培养物中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。
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性。此外，IL-1的亚慢性给药诱导行为、神经递质、激素和免疫变化，这些变化可能与某些精神疾病（如抑郁症）的机制有因果关系。
