UNLABELLED: Intestinal ischemia, frequently found in clinical states such as aortic bypass operations or hemorrhagic shock, is associated with loss of gut barrier function. Subsequent translocation of indigenous bacteria and endotoxin have been implicated as a major contributor to a systemic immuno-inflammatory response, which finally leads to multiple organ failure. There is increasing evidence that intestinal injury can result in the gut becoming a cytokine generating organ. This study was designed to show direct evidence of the gut as a major source of proinflammatory cytokines after intestinal ischemia and to further relate this cytokine response to the extent of intestinal ischemia/reperfusion. Additionally the potential role of the altered intestinal barrier function after intestinal ischemia for this cytokine response was investigated. METHODS: Rats were subjected to occlusion of the superior mesenteric artery for 45 min. (SMAO45), 75 min. (SMAO75), SMAO for 45 min. and 30 min. reperfusion (SMAO45/30), or sham SMAO, and then killed. Mucosal membranes from the terminal ileum were mounted in a Ussing chamber. E. coli C25 was added to the mucosal side of the stripped gut epithelium in half of the chambers. TNF and IL-6 levels on mucosal and serosal side of the stripped gut epithelium were assessed serially over 3 hrs. Gut barrier function was assessed by in vitro bacterial translocation (BT) and the transepithelial resistance (TER) of the mucosal membrane. RESULTS: The TNF response was greatest in the SMAO75 group, the IL-6 response in the SMAO75 and SMAO45/30 groups. In the absence of E. coli C25. IL-6 was produced to a greater extent on the serosal side, while addition of bacteria led to a significantly increased TNF/IL-6 response at the mucosal side of the stripped gut epithelium. BT was increased in SMAO75 and SMAO45/30 rats. Baseline TER was decreased in all experimental compared to sham SMAO groups. Although gut barrier function was impaired after intestinal ischemia/reperfusion there was no correlation between intestinal cytokine response and gut permeability. CONCLUSIONS: The gut becomes a cytokine liberating organ alter intestinal ischemia/reperfusion. This cytokine response is affected by certain conditions, but is not directly related to an impaired intestinal barrier function.
UNLABELLED: Intestinal ischemia, frequently found in clinical states such as aortic bypass operations or hemorrhagic shock, is associated with loss of gut barrier function. Subsequent translocation of indigenous bacteria and endotoxin have been implicated as a major contributor to a systemic immuno-inflammatory response, which finally leads to multiple organ failure. There is increasing evidence that intestinal injury can result in the gut becoming a cytokine generating organ. This study was designed to show direct evidence of the gut as a major source of proinflammatory cytokines after intestinal ischemia and to further relate this cytokine response to the extent of intestinal ischemia/reperfusion. Additionally the potential role of the altered intestinal barrier function after intestinal ischemia for this cytokine response was investigated. METHODS:Rats were subjected to occlusion of the superior mesenteric artery for 45 min. (SMAO45), 75 min. (SMAO75), SMAO for 45 min. and 30 min. reperfusion (SMAO45/30), or sham SMAO, and then killed. Mucosal membranes from the terminal ileum were mounted in a Ussing chamber. E. coli C25 was added to the mucosal side of the stripped gut epithelium in half of the chambers. TNF and IL-6 levels on mucosal and serosal side of the stripped gut epithelium were assessed serially over 3 hrs. Gut barrier function was assessed by in vitro bacterial translocation (BT) and the transepithelial resistance (TER) of the mucosal membrane. RESULTS: The TNF response was greatest in the SMAO75 group, the IL-6 response in the SMAO75 and SMAO45/30 groups. In the absence of E. coli C25. IL-6 was produced to a greater extent on the serosal side, while addition of bacteria led to a significantly increased TNF/IL-6 response at the mucosal side of the stripped gut epithelium. BT was increased in SMAO75 and SMAO45/30 rats. Baseline TER was decreased in all experimental compared to sham SMAO groups. Although gut barrier function was impaired after intestinal ischemia/reperfusion there was no correlation between intestinal cytokine response and gut permeability. CONCLUSIONS: The gut becomes a cytokine liberating organ alter intestinal ischemia/reperfusion. This cytokine response is affected by certain conditions, but is not directly related to an impaired intestinal barrier function.
Authors: Rebecca M Rentea; Jennifer L Liedel; Katherine Fredrich; Scott R Welak; Kirkwood A Pritchard; Keith T Oldham; Pippa M Simpson; David M Gourlay Journal: J Surg Res Date: 2012-06-01 Impact factor: 2.192
Authors: Rosanna Di Paola; Marta Menegazzi; Emanuela Mazzon; Tiziana Genovese; Concetta Crisafulli; Martina Dal Bosco; Zhenzhen Zou; Hisanori Suzuki; Salvatore Cuzzocrea Journal: Intensive Care Med Date: 2008-10-25 Impact factor: 17.440