The central role of hypothalamic inflammation in the acute illness response and cachexia.
The central role of hypothalamic inflammation in the acute illness response and cachexia.
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DOI：
10.1016/j.semcdb.2015.10.038
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发表时间：
2016-06
影响因子：
7.3
通讯作者：
Marks DL
中科院分区：
文献类型：
--
作者：
Burfeind KG;Michaelis KA;Marks DL
当受到各种炎症威胁的挑战时，全身的多个系统都会发生生理反应，以促进防御和生存。发烧、厌食和疲劳的组合被称为急性疾病反应，代表了对感染等刺激的适应性行为和生理反应。另一方面，恶病质是一种致命的、临床上具有挑战性的综合征，涉及厌食、疲劳和肌肉萎缩。这两个过程都是由炎症介质，包括细胞因子，趋化因子和免疫细胞。虽然恶病质的影响可以部分解释为疾病过程对消耗组织的直接影响，但越来越多的证据表明中枢神经系统（CNS）在恶病质中也起着重要的机制作用。在炎症应激的背景下，下丘脑整合来自外周系统的信号，其转化为神经内分泌扰动、改变的神经元信号传导和全局代谢紊乱。因此，我们将讨论下丘脑炎症如何成为急性疾病反应和恶病质的重要驱动因素，以及为什么这个器官具有独特的能力来产生和维持慢性炎症。首先，我们将重点关注下丘脑在饮食和感染刺激的急性反应中的作用。接下来，我们将讨论细胞因子在驱动体内平衡失调中的作用，导致肌肉萎缩、厌食和体重减轻。最后，我们将讨论慢性下丘脑炎症的机制和介质，包括内皮细胞，趋化因子和外周血白细胞。
When challenged with a variety of inflammatory threats, multiple systems across the body undergo physiological responses to promote defense and survival. The constellation of fever, anorexia, and fatigue is known as the acute illness response, and represents an adaptive behavioral and physiological reaction to stimuli such as infection. On the other end of the spectrum, cachexia is a deadly and clinically challenging syndrome involving anorexia, fatigue, and muscle wasting. Both of these processes are governed by inflammatory mediators including cytokines, chemokines, and immune cells. Though the effects of cachexia can be partially explained by direct effects of disease processes on wasting tissues, a growing body of evidence shows the central nervous system (CNS) also plays an essential mechanistic role in cachexia. In the context of inflammatory stress, the hypothalamus integrates signals from peripheral systems, which it translates into neuroendocrine perturbations, altered neuronal signaling, and global metabolic derangements. Therefore, we will discuss how hypothalamic inflammation is an essential driver of both the acute illness response and cachexia, and why this organ is uniquely equipped to generate and maintain chronic inflammation. First, we will focus on the role of the hypothalamus in acute responses to dietary and infectious stimuli. Next, we will discuss the role of cytokines in driving homeostatic disequilibrium, resulting in muscle wasting, anorexia, and weight loss. Finally, we will address mechanisms and mediators of chronic hypothalamic inflammation, including endothelial cells, chemokines, and peripheral leukocytes.