Gut damage during hemorrhagic shock: Effects on survival of oral or enteral interleukin-6

It has been reported that oral interleukin (IL)-6, without deleterious syst emic side effects, prevents bacteremia and gut epithelial apoptosis after h emorrhagic shock (HS) in rodents. The goal of this study was to explore pot ential benefit of oral or enteral IL-6 on the gut and, consequently, on sur vival in a long-term outcome model of HS in rats. In Study A, 20 rats (cont rol and IL-6, n = 10 per group) were anesthetized by spontaneous breathing of halothane and N2O. The left femoral vein and artery were cannulated. HIS was initiated with withdrawal of 3 mL of blood per 100 g body weight over 15 min, and mean arterial pressure was maintained at 40 to 50 mmHg for anot her 75 min (total HS 90 min) by blood withdrawal or infusion of Ringer's so lution. At HS 90 min, resuscitation included reinfusion of shed blood and a dditional Ringer's solution to restore normotension for 30 min. After awake ning at resuscitation time 30 min, the rats received either 300 units IL-6 or the same volume of vehicle (controls) injected into the stomach via a fe eding cannula. In Study B, 20 rats (control and IL-6, n = 10 per group), fa sted overnight, were prepared and treated as in Study A, except that HIS wa s initiated with withdrawal of 2 mL blood per 100 g over 10 min, and mean a rterial pressure was maintained at 35-40 mmHg. IL-6 rats received 3,000 uni ts IL-6 in 5 mL of normal saline injected directly into the ileum lumen 20 min after induction of shock and again at resuscitation time 60 min. Contro l rats received normal saline alone. In both studies, survival was observed to 72 h. In Study A, 7 of 10 rats in the control group and 5 of 10 in the IL-6 group survived to 72 h (NS). Macroscopic assessment of gut injury was not different between the two groups. In Study B, 6 of 10 rats survived to 72 h in each group. Frequency of bacteria growth in liver tissue of 72 h su rvivors was not different between the two groups. IL-6, administered into t he stomach or directly injected into the small intestine lumen, did not pro tect the gut from ischemic injury, nor did it improve survival following se vere HS in rats.