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Am J Physiol Gastrointest Liver Physiol (May 28, 2003). doi:10.1152/ajpgi.00177.2003
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Submitted on April 16, 2003
Accepted on May 16, 2003

IL-6 is essential for the development of gut barrier dysfunction after hemorrhagic shock and resuscitation in mice

Runkuan Yang1, Xiaonan Han1, Takashi Uchiyama1, Simon K. Watkins2, Arino Yaguchi1, Russell L. Delude3, and Mitchell P. Fink4*

1 Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2 Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
3 Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
4 Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

* To whom correspondence should be addressed. E-mail: finkmp{at}ccm.upmc.edu.

We sought to determine the role of IL-6 as a mediator of the alterations in gut barrier function that occur following hemorrhagic shock and resuscitation (HS/R). C57Bl/6 wild-type (WT) and IL-6 knockout (KO) mice on a C57Bl/6 background were subjected to either a sham procedure or HS/R. Organ and tissue samples were obtained 4 h after resuscitation. In WT mice, HS/R significantly increased ileal mucosal permeability to fluorescein isothiocyanate-labeled dextran (average molecular weight 4 kDa) and bacterial translocation to mesenteric lymph nodes. These alterations in gut barrier function were not observed in IL-6 KO animals. HS/R increased ileal steady-state mRNA levels for IL-6, TNF and IL-10 in WT but not in IL-6 KO mice. Ileal mucosal expression of the tight junction protein, ZO-1, decreased following HS/R in WT but not IL-6 KO mice. Collectively, these data support the view that expression of IL-6 is essential for the development of gut barrier dysfunction following HS/R.




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