Influence of continuous infusion of interleukin-1β on depression-related processes in mice:: corticosterone, circulating cytokines, brain monoamines, and cytokine mRNA expression
Influence of continuous infusion of interleukin-1β on depression-related processes in mice:: corticosterone, circulating cytokines, brain monoamines, and cytokine mRNA expression
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DOI：
10.1007/s00213-008-1166-z
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发表时间：
2008-08-01
影响因子：
3.4
通讯作者：
Hayley, Shawn
中科院分区：
文献类型：
--
作者：
Anisman, Hymie;Gibb, Julie;Hayley, Shawn
原理
免疫系统的激活通常以亚慢性或慢性的方式发生（例如，对细菌或病毒的侵害作出反应时）。然而，对细胞因子治疗效果的分析通常涉及急性治疗，关于亚慢性白细胞介素 - 1β（IL - 1β）给药对行为和中枢神经化学的影响，现有数据有限。
目的
在单次或重复推注IL - 1β或在数天内持续输注该细胞因子（通过Alzet微型泵）后，对IL - 1β治疗的几种外周和中枢效应进行了评估。
结果
在经过5天的IL - 1β治疗后，急性推注IL - 1β（1.0μg）对血浆皮质酮以及循环中的IL - 1β、IL - 6和肿瘤坏死因子 - α的影响减弱，尽管仍明显有较高程度的疾病症状。当IL - 1β（1.0或2.0μg/天）连续输注3天时，血浆皮质酮水平和疾病症状升高，但在治疗7天（亚慢性）后这些效应减弱。同样，IL - 1β治疗对运动活动的昼夜变化的影响在数天内减弱。尽管在治疗7天后细胞因子对行为和神经内分泌的影响减弱，但亚慢性IL - 1β输注改变了前额叶皮质和海马的血清素和去甲肾上腺素的利用，并且在这些区域内，IL - 1β、IL - 6、肿瘤坏死因子 - α及其受体，以及5 - HT2C、5 - HT1B受体和p11的信使核糖核酸（mRNA）表达增加。
讨论
研究结果表明，外周细胞因子输注显著影响中枢细胞因子mRNA表达，也影响5 - 羟色胺的周转，这可能导致IL - 1β引发的行为变化。
Rationale Activation of the immune system typically occurs on a subchronic or chronic basis (e.g., in response to bacterial or viral insults). However, analyses of the effects of cytokine treatments have typically involved acute treatments, and limited data are available concerning the behavioral and central neurochemical impact of subchronic interleukin-1 beta (IL-1 beta) administration.Objectives Several peripheral and central effects of IL-1 beta treatment were assessed following single or repeated bolus injections or after infusion of the cytokine (through Alzet minipumps) over several days.Results The impact of an acute bolus injection of IL-1 beta (1.0 mu g) on plasma corticosterone and on circulating IL-1 beta, IL-6, and TNF-alpha were diminished following 5-day IL-1 beta treatment, although high levels of sickness were still apparent. When IL-1 beta (1.0 or 2.0 mu g/day) was continuously infused over 3 days, plasma corticosterone and sickness were elevated, but these effects were attenuated after 7 days (subchronic) of treatment. As well, the effects of IL-1 beta treatment on diurnal variations of motor activity diminished over days. Despite the diminution of the behavioral and neuroendocrine effects of the cytokine after treatment 7 days, subchronic IL-1 beta infusion altered prefrontal cortical and hippocampal serotonin and norepinephrine utilization, and within these regions, the messenger RNA (mRNA) expression of IL-1 beta, IL-6, TNF-alpha, and their receptors, as well as that of 5-HT2C, 5-HT1B receptors, and p11, was increased.Discussion The findings indicate that peripheral cytokine infusion markedly influences central cytokine mRNA expression and also influences 5-HT turnover, which might contribute to behavioral changes elicited by IL-1 beta.