INTESTINAL CYTOKINE LIBERATION AFTER GUT ISCHEMIA IN THE RAT - INVESTIGATIONS IN THE USSING CHAMBER SYSTEM

Intestinal ischemia, frequently found in clinical states such as aorti c bypass operations or hemorrhagic shock, is associated with loss of g ut barrier function. Subsequent translocation of indigenous bacteria a nd endotoxin have been implicated as a major contributor to a systemic immune-inflammatory response, which finally leads to multiple organ f ailure. There is increasing evidence that intestinal injury can result in the gut becoming a cytokine generating organ. This study was desig ned to show direct evidence of the gut as a major source of proinflamm atory cytokines after intestinal ischemia and to further relate this c ytokine response to the extent of intestinal ischemia/reperfusion. Add itionally the potential role of the altered intestinal barrier functio n after intestinal ischemia for this cytokine response was investigate d. Methods: Rats were subjected to occlusion of the superior mesenteri c artery for 45 min. (SMAO45), 75 min. (SMAO75), SMAO for 45 min. and 30 min. reperfusion (SMAO45/30), or sham SMAO, and then killed. Mucosa l membranes from the terminal ileum were mounted in a Ussing chamber. E. coli C25 was added to the mucosal side of the stripped gut epitheli um 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 translocatio n (BT) and the transepithelial resistence (TER) of the mucosal membran e. 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. co li C25, IL-6 was produced to a greater extent on the serosal side, whi le addition of bacteria led to a significantly increased TNF/IL-6 resp onse at the mucosal side of the stripped gut epithelium. BT was increa sed in SMAO75 and SMAO45/30 rats. Baseline TER was decreased in all ex perimental compared to sham SMAO groups. Although gut barrier function was impaired after intestinal ischemia/reperfusion there was no corre lation between intestinal cytokine response and gut permeability. Conc lusions. The gut becomes a cytokine liberating organ after intestinal ischemia/reperfusion. This cytokine response is affected by certain co nditions, but is not directly related to an impaired intestinal barrie r function.