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. Weigand

Matthias Nahrendorf, Ralph Weissleder, Filip K. Swirski

Research output: Contribution to journal › Article › peer-review

328 Scopus citations

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
State	Published - 13 Mar 2015
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

@article{dedc4ea833754d529d1fe4e3aa600e1a,

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.\}",

year = "2015",

month = mar,

day = "13",

doi = "10.1126/science.aaa4268",

language = "English",

volume = "347",

pages = "1260--1265",

journal = "Science",

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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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T1 - Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis

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

N2 - 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.

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.

UR - https://www.scopus.com/pages/publications/84924787263

U2 - 10.1126/science.aaa4268

DO - 10.1126/science.aaa4268

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AN - SCOPUS:84924787263

SN - 0036-8075

VL - 347

SP - 1260

EP - 1265

JO - Science

JF - Science

IS - 6227

ER -

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

Abstract

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