Origin and Function of Stress-Induced IL-6 in Murine Models
Origin and Function of Stress-Induced IL-6 in Murine Models
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DOI：
10.1016/j.cell.2020.05.054
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发表时间：
2020-07-23
期刊：
影响因子：
64.5
通讯作者：
Wang, Andrew
中科院分区：
文献类型：
--
作者：
Qing, Hua;Desrouleaux, Reina;Wang, Andrew
人们早就知道，急性心理压力会降低宿主对多种疾病的炎症的适应性，但这种情况是如何发生的尚不完全清楚。使用小鼠模型，我们表明白介素 6 (IL-6) 是仅在急性应激下可诱导的主要细胞因子。应激诱导型 IL-6 是由棕色脂肪细胞以 β-3-肾上腺素能受体依赖性方式产生的。在应激期间，内分泌IL-6是通过肝糖异生介导高血糖所需的指导信号，这对于预测和促进“战斗或逃跑”反应是必要的。这种适应的代价是增加随后炎症挑战的死亡率。这些发现提供了对 IL-6 作为协调全身免疫代谢重编程的真正应激激素的个体发育和适应性目的的机制理解。这种脑-棕色脂肪-肝轴可能为棕色脂肪组织作为应激反应性内分泌器官提供新的见解，并为在炎症和神经精神疾病的治疗中针对该轴提供机制见解。
Acute psychological stress has long been known to decrease host fitness to inflammation in a wide variety of diseases, but how this occurs is incompletely understood. Using mouse models, we show that interleukin-6 (IL-6) is the dominant cytokine inducible upon acute stress alone. Stress-inducible IL-6 is produced from brown adipocytes in a beta-3-adrenergic-receptor-dependent fashion. During stress, endocrine IL-6 is the required instructive signal for mediating hyperglycemia through hepatic gluconeogenesis, which is necessary for anticipating and fueling "fight or flight" responses. This adaptation comes at the cost of enhancing mortality to a subsequent inflammatory challenge. These findings provide a mechanistic understanding of the ontogeny and adaptive purpose of IL-6 as a bona fide stress hormone coordinating systemic immunome-tabolic reprogramming. This brain-brown fat-liver axis might provide new insights into brown adipose tissue as a stress-responsive endocrine organ and mechanistic insight into targeting this axis in the treatment of inflammatory and neuropsychiatric diseases.