Influence of gut microflora on mesenteric lymph cytokine production in rats with hemorrhagic shock

Objective: The aim of the present study was to test the hypothesis that the resident gut microflora play a role in modulating gut cytokine production under normal circumstances and in response to tissue injury with or without hemorrhagic shock. Methods: The postnodal lymph was collected from the main mesenteric lymphatic channel 1 hour before, during (1.5 hours), and hourly for 6 hours after 90 minutes of sham or actual hemorrhagic shock (30 mm Hg) in the following three groups of rats, all of which had laparotomies and vascular instrumentation: rats with a normal gut flora (NF), rats whose gut flora had been decontaminated with oral antibiotics (AD), and rats with Escherichia coli C25 intestinal overgrowth (MA). Interleukin (IL)-6 and TNF levels in the mesenteric lymph were measured using cytokine-dependent cellular assays. Endotoxin levels and endotoxin-neutralizing capacity in the lymph were also measured. Results: Mesenteric lymph IL-6 levels in the laparotomized MA-sham animals were significantly elevated compared with NF-sham animals at 2 to 4 hours (p < 0.05) and at 5 and 6 hours after sham shock (p < 0.01). Similarly, IL-6 levels in laparotomized AD-shock animals were increased when compared with NF-shock animals 3 hours after shock (p < 0.001). Lymph tumor necrosis factor bioactivity, although present in all surgically manipulated groups, was scarcely detectable in untouched animals. Endotoxin-neutralizing capacity was significantly impaired in shocked animals compared with untouched animals. Conclusion: Changes in the gut microflora modulate the gut cytokine production after tissue injury with or without hemorrhagic shock, with intestinal bacterial overgrowth leading to the greatest increase in mesenteric lymph IL-6 levels.