gms | German Medical Science

131. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

25.03. - 28.03.2014, Berlin

Interleukin (IL)-3 triggers septic shock

Meeting Abstract

  • Georg F. Weber - Universitätsklinikum Dresden, Klinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden
  • Nuh N. Rahbari - Universitätsklinikum Dresden, Klinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden
  • Ingo Hilgendorf - Massachusetts General Hospital, Harvard Medical School, Center for Systems Biology, Boston
  • Yoshiko Iwamoto - Massachusetts General Hospital, Harvard Medical School, Center for Systems Biology, Boston
  • Florian Uhle - Universitätsklinikum Giessen, Klinik für Anästhesiologie, Gießen
  • Markus A. Weigand - Universitätsklinikum Giessen, Klinik für Anästhesiologie, Gießen
  • Matthias Nahrendorf - Massachusetts General Hospital, Harvard Medical School, Center for Systems Biology, Boston
  • Jürgen Weitz - Universitätsklinikum Dresden, Klinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden
  • Ralph Weissleder - Massachusetts General Hospital, Harvard Medical School, Center for Systems Biology, Boston
  • Filip K. Swirski - Massachusetts General Hospital, Harvard Medical School, Center for Systems Biology, Boston

Deutsche Gesellschaft für Chirurgie. 131. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 25.-28.03.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. Doc14dgch536

doi: 10.3205/14dgch536, urn:nbn:de:0183-14dgch5360

Published: March 21, 2014

© 2014 Weber et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Introduction: Sepsis is a frequently fatal condition characterized by an uncontrolled host reaction to microbial infection. Human studies have shown that sepsis is associated with excessive production of inflammatory cytokines – an event known as the cytokine storm. Clinical trials targeting inflammatory mediators have failed, however, creating an urgent need for a better fundamental understanding of sepsis’ pathophysiology.

Material and methods: Sepsis induction by Cecal Ligation and Puncture (CLP) and analysis of the initial immune response. Ex vivo and in vitro studies for the analysis of cytokine production. Analysis of expression rates, immunofluorescence histological as well as fate mapping analysis for detection of the site of IL-3 production.

Results: Here we show that IL-3 is an essential inducer of inflammation in sepsis. Although almost undetectable in the steady state, IL-3 expression was pronounced in response to microbial infection in a mouse model. Within hours after sepsis induction the expression rates of IL-3 were elevated in the spleen. The cellular source of IL-3 were the recently described innate response activator (IRA) B cells which arose from peritoneal B1 cells via direct recognition of bacteria at the site of infection. IL-3 contributed substantially to the ensuing cytokine storm by leading to the production of abundant IL-1β, IL-6 and TNFα. As a consequence, IL-3 precipitated multi-organ damage, septic shock, and death.

Conclusion: Altogether, this study enriches our understanding of the initial immune activation during sepsis, and identifies IL-3 as a potential therapeutic target for the treatment of sepsis.