Interleukin-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury

Christian Hierholzer, Jörg C. Kalff, Laurel Omert, Katsuhiko Tsukada, J. Eric Loeffert, Simon C. Watkins, Timothy R. Billiar, David J. Tweardy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

Hemorrhagic shock (HS) initiates an inflammatory cascade that includes the production of cytokines and recruitment of neutrophils (PMN) and may progress to organ failure, inducing acute respiratory distress syndrome (ARDS). To examine the hypothesis that interleukin-6 (IL-6) contributes to PMN infiltration and lung damage in HS, we examined the lungs of rats subjected to unresuscitated and resuscitated HS for the production of IL-6 and activation of Stat3. Using semiquantitative RT-PCR, we found a striking increase in IL-6 mRNA levels only in resuscitated HS, with peak levels observed 1 h after initiation of resuscitation. Increased IL-6 protein expression was localized to bronchial and alveolar cells. Electrophoretic mobility shift assay of protein extracts from shock lungs exhibited an increase in Stat3 activation with kinetics similar to IL-6 mRNA. In situ DNA binding assay determined Stat3 activation predominantly within alveoli. Intratracheal instillation of IL-6 alone into normal rats resulted in PMN infiltration into lung interstitium and alveoli, marked elevation of bronchoalveolar lavage cellularity, and increased wet-to-dry ratio. These findings indicate that IL-6 production and Stat3 activation occur early in HS and may contribute to PMN-mediated lung injury, including ARDS after HS.

Original languageEnglish
Pages (from-to)L611-L621
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume275
Issue number3 19-3
DOIs
StatePublished - Sep 1998
Externally publishedYes

Keywords

  • Acute inflammation
  • Acute respiratory distress syndrome
  • Cytokines
  • Signal transducers and activators of transcription

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