Wieczorek Marek, Dunn Adrian J
Department of Neurophysiology, University of Lodz, Poland.
Brain Behav Immun. 2006 Sep;20(5):477-87. doi: 10.1016/j.bbi.2005.10.001. Epub 2005 Dec 2.
Peripheral administration of interleukin-1 (IL-1) is known to activate the hypothalamo-pituitary-adrenal axis (HPA axis) and brain noradrenergic systems. We studied the relationship between these responses using in vivo microdialysis to assess the release of hypothalamic norepinephrine (NE), while simultaneously sampling blood for ACTH and corticosterone, and monitoring body temperature and behavior in freely moving rats. Rats were implanted with microdialysis probes in the medial hypothalamus, with intravenous catheters, and with telethermometers in the abdomen. Each rat was injected with saline and IL-1beta (1 microg ip) in random order, monitoring microdialysate NE, body temperature and plasma ACTH and corticosterone for 2-4 h after injection. Saline injections were followed by transient increases in microdialysate NE and in plasma ACTH and corticosterone. IL-1beta injections resulted in prolonged elevations of microdialysate NE, as well as plasma ACTH and corticosterone, and body temperature. IL-1beta also induced shivering and a prolonged depression of locomotor activity. Pretreatment with indomethacin (10 mg/kg sc) prevented the IL-1beta-induced increases in body temperature and the apparent increase in hypothalamic NE release, but only attenuated the IL-1beta-induced shivering and the increase in plasma ACTH. The results indicate a close temporal relationship between the release of NE and HPA axis activation. Such a relationship is also supported by the similar effects of indomethacin pretreatment on NE and ACTH. The shivering is likely involved in the increase in body temperature, but indomethacin only attenuated the shivering while it blocked the fever. However, the effects of indomethacin clearly indicate that neither the increase in body temperature nor the increase in hypothalamic NE release was essential for HPA axis activation. These results suggest that hypothalamic NE is involved in the IL-1-induced HPA axis activation, but that this is not the only mechanism by which the HPA axis is activated by intraperitoneally injected IL-1.
已知外周给予白细胞介素-1（IL-1）可激活下丘脑-垂体-肾上腺轴（HPA轴）和脑去甲肾上腺素能系统。我们利用体内微透析评估下丘脑去甲肾上腺素（NE）的释放，同时采集血液检测促肾上腺皮质激素（ACTH）和皮质酮，并监测自由活动大鼠的体温和行为，以此研究这些反应之间的关系。给大鼠在内侧下丘脑植入微透析探针、静脉导管，并在腹部植入遥测温度计。每只大鼠按随机顺序注射生理盐水和IL-1β（1微克，腹腔注射），注射后2 - 4小时监测微透析液中的NE、体温以及血浆ACTH和皮质酮。注射生理盐水后，微透析液中的NE以及血浆ACTH和皮质酮出现短暂升高。注射IL-1β导致微透析液中的NE、血浆ACTH和皮质酮以及体温长时间升高。IL-1β还诱发寒战并使运动活动长时间受到抑制。用吲哚美辛（10毫克/千克，皮下注射）预处理可防止IL-1β诱导的体温升高以及下丘脑NE释放的明显增加，但仅减弱了IL-1β诱导的寒战和血浆ACTH的增加。结果表明NE释放与HPA轴激活之间存在密切的时间关系。吲哚美辛预处理对NE和ACTH的类似作用也支持了这种关系。寒战可能与体温升高有关，但吲哚美辛仅减弱了寒战，却阻断了发热。然而，吲哚美辛的作用清楚地表明，体温升高和下丘脑NE释放增加对于HPA轴激活都不是必需的。这些结果提示下丘脑NE参与了IL-1诱导的HPA轴激活，但这不是腹腔注射IL-1激活HPA轴的唯一机制。
