Weber, GeorgChousterman, BenjaminHe, ShunFenn, AshleyNairz, ManfredAnzai, AtsushiBrenner, ThorstenUhle, FlorianIwamoto, YoshikoRobbins, ClintonNoiret, LoretteMaier, SarahZönnchen, TinaRahbari, NuhSchölch, SebastianAmeln, Anne Klotzsche-vonChavakis, TriantafyllosJürgen WeitzHofer, StefanWeigand, MarkusNahrendorf, MatthiasWeissleder, RalphSwirski, Filip2019-09-212015Weber, G. F., B. G. Chousterman, S. He, A. M. Fenn, M. Nairz, A. Anzai, T. Brenner, et al. 2015. “Interleukin-3 Amplifies Acute Inflammation and Is a Potential Therapeutic Target in Sepsis.” Science 347 (6227): 1260–65. https://doi.org/10.1126/science.aaa4268.0036-80751095-9203http://nrs.harvard.edu/urn-3:HUL.InstRepos:41384301Sepsis is a frequently fatal condition characterized by an uncontrolled and harmful host reaction to microbial infection. Despite the prevalence and severity of sepsis, we lack a fundamental grasp of its pathophysiology. Here we report that the cytokine interleukin-3 (IL-3) potentiates inflammation in sepsis. Using a mouse model of abdominal sepsis, we showed that innate response activator B cells produce IL-3, which induces myelopoiesis of Ly-6C(high) monocytes and neutrophils and fuels a cytokine storm. IL-3 deficiency protects mice against sepsis. In humans with sepsis, high plasma IL-3 levels are associated with high mortality even after adjusting for prognostic indicators. This study deepens our understanding of immune activation, identifies IL-3 as an orchestrator of emergency myelopoiesis, and reveals a new therapeutic target for treating sepsis.en-USJournal Article2019-09-2110.1126/science.aaa4268