Infection as a stressor: a cytokine-mediated activation of the hypothalamo-pituitary-adrenal axis?
Infection as a stressor: a cytokine-mediated activation of the hypothalamo-pituitary-adrenal axis?
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感染作为应激源：细胞因子介导的下丘脑-垂体-肾上腺轴激活？
DOI：
10.1002/9780470514368.ch11
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Dunn,AJ
中科院分区：
文献类型：
--
作者：
Dunn,AJ
感染与促肾上腺皮质激素（ACTH）和皮质酮的血浆浓度增加有关。下丘脑-垂体-肾上腺（HPA）反应也被观察到与免疫刺激，而不是感染。虽然这种反应被认为是由淋巴细胞分泌的ACTH介导的，但免疫刺激引起的肾上腺皮质激活需要功能性垂体。免疫刺激激活HPA轴的最可能机制涉及淋巴细胞产生细胞因子。主要候选者是白细胞介素1（IL-1），因为IL-1的产生遵循免疫系统的激活，并且IL-1给药是HPA轴的有效激活剂。然而，其他细胞因子，如肿瘤坏死因子，也可能参与。大多数免疫刺激和IL-1也激活外周和中枢去甲肾上腺素能神经元。在体内，IL-1诱导的HPA轴蛋白激活取决于促肾上腺皮质激素释放因子（CRF）的分泌、完整的垂体和支配下丘脑室旁核（PVN）中含CRF神经元的腹侧去甲肾上腺素能束。除了升高体温外，IL-1的给药还能诱发大鼠和小鼠的许多行为反应，包括厌食、睡眠时间增加、减少对新物体和其他动物的研究、增加防御性退缩和其他疾病特征性行为。其中一些反应可以被CRF拮抗剂逆转，并被CRF给药模拟。因此，IL-1的内源性产生可以解释疾病的一系列生理和行为反应特征。然而，缺乏IL-1介导患病动物这些反应的确切证据。
Infections are associated with increased plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone. Hypothalamo‐pituitary‐adrenal (HPA) responses have also been observed with immunological stimuli that are not infective. Although such responses have been suggested to be mediated by ACTH secreted by lymphocytes, adrenocortical activation by immunological stimuli requires a functional pituitary. The most likely mechanism by which immunological stimuli activate the HPA axis involves production of cytokines by lymphocytes. The prime candidate is interleukin 1 (IL‐1), because IL‐1 production follows activation of the immune system and 1L‐1 administration is a potent activator of the HPA axis. However, other cytokines, such as tumour necrosis factor, may also be involved. Most immunological stimuli and IL‐1 also activate both peripheral and central noradrenergic neurons. IL‐1‐induced activation of the HPA axisin vivodepends upon secretion of corticotropin‐releasing factor (CRF), an intact pituitary, and the ventral noradrenergic bundle which innervates the CRF‐containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Besides elevating body temperature, administration of IL‐1 elicits a number of behavioural responses in rats and mice, including anorexia, increased sleep time, decreased investigation of novel objects and other animals, increased defensive withdrawal and other behaviours characteristic of sickness. Some of these responses can be reversed by CRF‐antagonists and mimicked by CRF administration. Thus, endogenous production of IL‐1 can account for a range of physiological and behavioural responses characteristic of sickness. Nevertheless, definitive evidence that IL‐1 mediates these responses in sick animals is lacking.