Alterations in intestinal bacterial flora modulate the systemic cytokine response to hemorrhagic shock

To test the hypothesis that the resident gut flora plays an active role in modulating the cytokine response to hemorrhagic shock, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured from the following three groups of rats before, immediately after, and 3, 8, or 24 h post-hemorrhagic shock (90 min at 30 mmHg)/sham shock: 1) rats with a normal gut flora (NF), 2) rats whose gut flora had been decontaminated with oral antibiotics (AD), and 3) rats with intestinal overgrowth with E. coli. In all three groups, portal and systemic TNF and IL-6 levels were 2- to 10-fold higher in the shock than the sham-shock rats (P < 0.05), with the highest TNF and IL-6 levels observed in the rats that were colonized with Escherichia coli (P < 0.05 vs. AD and NF). TNF levels were higher in the NF than the AD groups at 3 and 8 h postshock. The present study suggests that changes in the gut microflora modulate the systemic cytokine response to hemorrhagic shock with intestinal bacterial overgrowth leading to the greatest increase in plasma IL-6 and TNF levels.