Impaired gut contractility following hemorrhagic shock is accompanied by IL-6 and G-CSF production and neutrophil infiltration

Christian Hierholzer, Jörg C. Kalff, Arup Chakraborty, Simon C. Watkins, Timothy R. Billiar, Anthony J. Bauer, David J. Tweardy

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45 Scopus citations


Recovery from hemorrhagic shock (HS) is frequently accompanied by bowel stasis. The aim of this study was to examine whether or not HS initiates an inflammatory response that includes production of cytokines, specifically G-CSF and interleukin-6 (IL-6), and recruitment of leukocytes within the intestinal muscularis which contribute to impaired muscle contractility. Sprague-Dawley rats were subjected to HS (MAP 40 mm Hg for 156 min) followed by resuscitation, and then they were killed at 4 hr. Shock animals demonstrated accumulation of PMNs in the jejunal muscularis and decreased spontaneous and bethanechol-stimulated muscle contractility. Semiquantitative RT-PCR demonstrated elevated levels of IL-6 and G-CSF mRNA in shock animals in full-thickness jejunum and in mucosa and muscularis layers compared to sham controls. Immunostaining demonstrated increased IL-6 protein production within the muscularis externa and submucosa. In situ hybridization studies localized G-CSF mRNA production to the submucosa. Gel shift assays revealed increased NF-κB and Stat3 activity in full-thickness jejunum and jejunal layers of shock animals. Activation of Stat3 also was demonstrated in normal muscularis tissue exposed to IL-6 and G-CSF in vitro. IL-6 and G-CSF are produced in the muscularis and mucosa layers of the gut in HS where they may contribute to PMN recruitment and smooth muscle dysfunction.

Original languageEnglish
Article number228836
Pages (from-to)230-241
Number of pages12
JournalDigestive Diseases and Sciences
Issue number2
StatePublished - 2001
Externally publishedYes


  • Inflammation
  • Nuclear factor-κB
  • Signal transducers and activators of transcription protein 3


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