美国耶鲁大学医学院 Andrew Wang与Ruslan Medzhitov研究团队的一项最新研究揭示了GDF15是一种炎症诱导的组织耐受中枢介质。该项研究成果发表在2019年8月22日出版的《细胞》上。

该团队研究了GDF15在细菌和病毒感染中的作用。发现炎症诱导的GDF15, GDF15对于细菌和病毒感染以及脓毒症的存活都是必要的。GDF15的保护作用在很大程度上不依赖于病原体控制或炎症反应的程度，表明其在疾病耐受中发挥作用。事实上，我们发现GDF15是肝脏交感神经流出和甘油三酯代谢所必需的。未能保护血浆甘油三酯水平的下限与心功能受损和体温维持有关，这些影响可以通过外源性脂类药物来挽救。总之，GDF15可以在炎症条件下被诱导表达，并通过调控甘油三酯的代谢使得宿主能够耐受细菌和病毒的感染。

研究人员表示，生长分化因子15 (GDF15)是一种与炎症相关的激素，其生物学意义尚不明确。

附：英文原文

Title: GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance

Author:Harding H. Luan,Andrew Wang,Brandon K. Hilliard,Fernando Carvalho

Connor E. Rosen,Amy M. Ahasic,Erica L. Herzog,Insoo Kang,Margaret A. Pisani,Shuang Yu,Cuiling Zhang,Aaron M. Ring,Lawrence H. Young,Ruslan Medzhitov

Issue&Volume: Volume 178 Issue 5

Abstract: Growth and differentiation factor 15 (GDF15) is an inflammation-associated hormone with poorly defined biology. Here, we investigated the role of GDF15 in bacterial and viral infections. We found that inflammation induced GDF15, and that GDF15 was necessary for surviving both bacterial and viral infections, as well as sepsis. The protective effects of GDF15 were largely independent of pathogen control or the magnitude of inflammatory response, suggesting a role in disease tolerance. Indeed, we found that GDF15 was required for hepatic sympathetic outflow and triglyceride metabolism. Failure to defend the lower limit of plasma triglyceride levels was associated with impaired cardiac function and maintenance of body temperature, effects that could be rescued by exogenous administration of lipids. Together, we show that GDF15 coordinates tolerance to inflammatory damage through regulation of triglyceride metabolism.

DOI: https://doi.org/10.1016/j.cell.2019.07.033

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30832-3