The role of adrenal gland microenvironment in the HPA axis function and dysfunction during sepsis
The role of adrenal gland microenvironment in the HPA axis function and dysfunction during sepsis
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DOI：
10.1016/j.mce.2014.12.019
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发表时间：
2015-06-15
影响因子：
4.1
通讯作者：
Bornstein, Stefan R.
中科院分区：
文献类型：
--
作者：
Kanczkowski, Waldemar;Sue, Mariko;Bornstein, Stefan R.
细菌或病毒感染引起的败血症和感染性休克仍然是世界范围内的主要健康问题。尽管经过了几十年的密集研究和医疗护理的改进，严重的脓毒症与高死亡率有关。肾上腺糖皮质激素和儿茶酚胺的快速激活是应激反应的基本组成部分，对宿主的生存至关重要。然而，在许多危重患者中，肾上腺的这种动态平衡功能经常受到损害。在这些患者中，血浆促肾上腺皮质激素(ACTH)和皮质醇的水平往往是分离的。这归因于肾上腺内非ACTH因子如细胞因子的刺激作用，以及最近皮质醇代谢下降和ACTH合成受抑。脓毒症时下丘脑-垂体-肾上腺(HPA)轴功能的调节是一个复杂的过程，涉及中枢神经系统(CNS)和肾上腺水平的各种免疫和神经内分泌相互作用。肾上腺内多种细胞类型和系统的协调相互作用参与了肾上腺糖皮质激素的持续产生。本文描述并讨论了最近有关脓毒症时肾上腺微环境的作用的实验结果，包括肾上腺血管和免疫-肾上腺在失控的HPA轴上的串扰。综上所述，除了皮质醇分解减少和相关的ACTH抑制外，脓毒症介导的免疫-肾上腺交织反应的慢性激活和血管功能障碍可能是脓毒症患者HPA轴调节失调的原因之一。(C)2014爱思唯尔爱尔兰有限公司。保留所有权利。
Sepsis and septic shock in response to bacterial or viral infections remain the major health problem worldwide. Despite decades of intensive research and improvements in medical care, severe sepsis is associated with high mortality. Rapid activation of the adrenal gland glucocorticoid and catecholamine production is a fundamental component of the stress response and is essential for survival of the host. However, in many critically ill patients this homeostatic function of the adrenal gland is often impaired. In these patients, plasma levels of adrenocorticotropic hormone (ACTH) and cortisol are often dissociated. This has been attributed to the stimulatory action of non-ACTH factors within the adrenal gland such as cytokines, and recently with decreased cortisol metabolism and suppressed ACTH synthesis. Regulation of the hypothalamus-pituitary-adrenal (HPA) axis function during sepsis is a complex process which involves various immune and neuroendocrine interactions occurring at the levels of the central nervous system (CNS) and the adrenal gland. A coordinated interaction of numerous cell types and systems within the adrenal gland is involved in the sustained adrenal glucocorticoid production. This review article describes and discusses recent experimental findings regarding the role of adrenal gland microenvironment including the adrenal vasculature and the immune-adrenal crosstalk in the disregulated HPA axis during sepsis conditions. In summary, in addition to the reduced cortisol breakdown and related ACTH suppression, sepsis-mediated chronic activation of the immune-adrenal crosstalk and vascular dysfunction may contribute to the HPA axis dysregulation found in septic patients. (C) 2014 Elsevier Ireland Ltd. All rights reserved.