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

Science. 2015 Mar 13;347(6227):1260-5. doi: 10.1126/science.aaa4268.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Inflammation
  • Interleukin-3 / blood
  • Interleukin-3 / immunology*
  • Interleukin-3 / metabolism
  • Lipopolysaccharides / immunology
  • Lymphoid Tissue / immunology
  • Mice
  • Mice, Inbred BALB C
  • Monocytes / immunology
  • Myelopoiesis
  • Neutrophils / immunology
  • Peritonitis / immunology
  • Peritonitis / pathology
  • Prognosis
  • Sepsis / immunology*
  • Sepsis / mortality
  • Sepsis / pathology
  • Sepsis / therapy


  • Cytokines
  • IL3 protein, human
  • Interleukin-3
  • Lipopolysaccharides