小柯机器人

美国耶鲁大学医学院Andrew Wang课题组的最新研究揭示了小鼠中压力引发IL-6的起源与功能。2020年6月30日，《细胞》在线发表了这一成果。

使用小鼠模型，研究人员发现白介素6（IL-6）是只在急性应激时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-肾上腺素受体依赖性方式产生的。在压力期间，内分泌型IL-6是通过肝糖异生介导高血糖所必需的指导性信号，这对于“战斗或逃跑”反应是必需的。这种适应的代价在于：随后炎症导致的死亡率会增加。

这些发现表明，IL-6是真正的应激激素，从而协调全身性免疫代谢重编程。这种大脑-棕色脂肪-肝信号轴可能为棕色脂肪组织作为压力响应性内分泌器官提供新的见识，并为在炎症和神经精神疾病治疗中靶向这一信号轴提供了机制性理解。

据悉，长期以来，人们都知道急性心理压力会降低宿主对多种疾病炎症的适应能力，但这种情况的发生方式尚不完全清楚。

附：英文原文

Title: Origin and Function of Stress-Induced IL-6 in Murine Models

Author: Hua Qing, Reina Desrouleaux, Kavita Israni-Winger, Yann S. Mineur, Nia Fogelman, Cuiling Zhang, Saleh Rashed, Noah W. Palm, Rajita Sinha, Marina R. Picciotto, Rachel J. Perry, Andrew Wang

Issue&Volume: 2020-06-30

Abstract: 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 immunometabolic 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.

DOI: 10.1016/j.cell.2020.05.054

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30687-5#