Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
Pharmacol Rep. 2011;63(6):1393-403. doi: 10.1016/s1734-1140(11)70703-4.
Interleukin-1β (IL-1β) level is modulated during multiple stress reactions both in brain structures involved in hypothalamic-pituitary-adrenal (HPA) axis regulation and peripheral systems. Multiple distinct stressors induce different IL-1β and HPA axis responses. The purpose of the present study was to determine if the effect of prior repeated restraint stress on IL-1β levels in prefrontal cortex, hippocampus, hypothalamus and plasma may have an impact on alterations induced in HPA axis responses. Experiments were performed on male Wistar rats which were exposed to 10 min restraint stress twice a day for 3 days. Twenty four hours after the last stress period rats were restrained for 10 min and decapitated at 0, 1, 2 or 3 h after cessation of stress. Control rats were injected ip with saline and some of experimental groups with IL-1β receptor antagonist (IL-1ra). After rapid decapitation, trunk blood was collected and prefrontal cortex, hippocampus and hypothalamus were excised and frozen. Interleukin-1β, adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were determined in plasma using commercially available kits and IL-1β levels in brain structures samples were analyzed by western blot procedure. Repeated restraint for 3 days alone did not alter resting plasma levels of IL-1β, and moderately augmented plasma ACTH and CORT levels and IL-1β content in brain structures 24 h after the last restraint. IL-1β antagonist abolished the increase in plasma levels of IL-1β, ACTH and CORT as well as IL-1β in brain structures in response to repeated stress and also reduced these changes induced by 10 min stress. This suggests the selectivity of IL-1β receptors in central and peripheral mechanisms modulating the stress-induced HPA axis responses. These results indicate that repeated stress markedly increases IL-1β production in brain structures involved in HPA axis regulation. The present results support the role of brain and peripheral IL-1β in adaptation of HPA response during prolonged stress.
白细胞介素-1β（IL-1β）水平在涉及下丘脑-垂体-肾上腺（HPA）轴调节的脑结构和外周系统的多种应激反应中受到调节。多种不同的应激源诱导不同的 IL-1β 和 HPA 轴反应。本研究的目的是确定先前反复束缚应激对前额叶皮层、海马体、下丘脑和血浆中 IL-1β 水平的影响是否会影响 HPA 轴反应的改变。实验在雄性 Wistar 大鼠中进行，这些大鼠每天接受两次 10 分钟的束缚应激，共 3 天。最后一次应激后 24 小时，大鼠被束缚 10 分钟，并在应激停止后 0、1、2 或 3 小时断头。对照大鼠腹腔注射生理盐水，部分实验组注射白细胞介素-1β受体拮抗剂（IL-1ra）。快速断头后，采集躯干血液，切除前额叶皮层、海马体和下丘脑并冷冻。使用市售试剂盒测定血浆中白细胞介素-1β、促肾上腺皮质激素（ACTH）和皮质酮（CORT）水平，采用 Western blot 法分析脑结构样品中的白细胞介素-1β水平。单独重复束缚 3 天不会改变静息状态下血浆中 IL-1β的水平，而适度增加了最后一次束缚后 24 小时血浆中 ACTH 和 CORT 的水平以及脑结构中的 IL-1β含量。IL-1β 拮抗剂消除了重复应激对血浆中 IL-1β、ACTH 和 CORT 以及脑结构中 IL-1β水平的增加，也减少了 10 分钟应激引起的这些变化。这表明 IL-1β 受体在中枢和外周机制中具有选择性，调节应激诱导的 HPA 轴反应。这些结果表明，重复应激显著增加了参与 HPA 轴调节的脑结构中 IL-1β 的产生。本研究结果支持脑和外周 IL-1β 在长期应激期间 HPA 反应适应中的作用。
