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. Weigand; Matthias Nahrendorf; Ralph Weissleder; Filip K. Swirski

doi:10.1126/science.aaa4268

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 journal › Article › peer-review

200 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-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.

Original language	English
Pages (from-to)	1260-1265
Number of pages	6
Journal	Science
Volume	347
Issue number	6227
DOIs	https://doi.org/10.1126/science.aaa4268
Publication status	Published - 2015 Mar 13
Externally published	Yes

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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

Weber, GF, Chousterman, BG, He, S, Fenn, AM, Nairz, M, Anzai, A, Brenner, T, Uhle, F, Iwamoto, Y, Robbins, CS, Noiret, L, Maier, SL, Zönnchen, T, Rahbari, NN, Schölch, S, Ameln, AKV, Chavakis, T, Weitz, J, Hofer, S, Weigand, MA, Nahrendorf, M, Weissleder, R & Swirski, FK 2015, 'Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis', Science, vol. 347, no. 6227, pp. 1260-1265. https://doi.org/10.1126/science.aaa4268

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title = "Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis",

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.",

author = "Weber, {Georg F.} and Chousterman, {Benjamin G.} and Shun He and Fenn, {Ashley M.} and Manfred Nairz and Atsushi Anzai and Thorsten Brenner and Florian Uhle and Yoshiko Iwamoto and Robbins, {Clinton S.} and Lorette Noiret and Maier, {Sarah L.} and Tina Z{\"o}nnchen and Rahbari, {Nuh N.} and Sebastian Sch{\"o}lch and Ameln, {Anne Klotzsche Von} and Triantafyllos Chavakis and J{\"u}rgen Weitz and Stefan Hofer and Weigand, {Markus A.} and Matthias Nahrendorf and Ralph Weissleder and Swirski, {Filip K.}",

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AU - Weber, Georg F.

AU - Chousterman, Benjamin G.

AU - He, Shun

AU - Fenn, Ashley M.

AU - Nairz, Manfred

AU - Anzai, Atsushi

AU - Brenner, Thorsten

AU - Uhle, Florian

AU - Iwamoto, Yoshiko

AU - Robbins, Clinton S.

AU - Noiret, Lorette

AU - Maier, Sarah L.

AU - Zönnchen, Tina

AU - Rahbari, Nuh N.

AU - Schölch, Sebastian

AU - Ameln, Anne Klotzsche Von

AU - Chavakis, Triantafyllos

AU - Weitz, Jürgen

AU - Hofer, Stefan

AU - Weigand, Markus A.

AU - Nahrendorf, Matthias

AU - Weissleder, Ralph

AU - Swirski, Filip K.

PY - 2015/3/13

Y1 - 2015/3/13

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AB - 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.

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

Abstract

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