Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis

Georg F. Weber, Benjamin G. Chousterman, Shun He, Ashley M. Fenn, Manfred Nairz, Atsushi Anzai, Thorsten Brenner, Florian Uhle, Yoshiko Iwamoto, Clinton S. Robbins, Lorette Noiret, Sarah L. Maier, Tina Zönnchen, Nuh N. Rahbari, Sebastian Schölch, Anne Klotzsche Von Ameln, Triantafyllos Chavakis, Jürgen Weitz, Stefan Hofer, Markus A. WeigandMatthias Nahrendorf, Ralph Weissleder, Filip K. Swirski

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Sepsis 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-6Chigh 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.

Original languageEnglish
Pages (from-to)1260-1265
Number of pages6
JournalScience
Volume347
Issue number6227
DOIs
Publication statusPublished - 2015 Mar 13

ASJC Scopus subject areas

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    Weber, G. F., Chousterman, B. G., He, S., Fenn, A. M., Nairz, M., Anzai, A., Brenner, T., Uhle, F., Iwamoto, Y., Robbins, C. S., Noiret, L., Maier, S. L., Zönnchen, T., Rahbari, N. N., Schölch, S., Ameln, A. K. V., Chavakis, T., Weitz, J., Hofer, S., ... Swirski, F. K. (2015). Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis. Science, 347(6227), 1260-1265. https://doi.org/10.1126/science.aaa4268