Effects of interleukin-1alpha administration on intestinal ischemia and reperfusion injury, mucosal permeability, and bacterial translocation in burn and sepsis.
OBJECTIVE
To evaluate the effect of interleukin-1alpha (IL-1alpha) on the mesenteric circulation, intestinal mucosal integrity, and bacterial translocation in a burn/endotoxemia chronic porcine model.


BACKGROUND
Major burn and sepsis are associated with a high mortality, ischemia/reperfusion injury to the intestine, and an increased rate of bacterial translocation. Pathologic alterations of IL-1 synthesis, degradation, and binding to receptors have been reported. Manipulation of IL-1-mediated effects might be of therapeutic utility.


METHODS
Twenty-one female pigs were instrumented with an ultrasonic flow probe on the superior mesenteric artery and a catheter into the superior mesenteric vein. After 5 days, all animals were anesthetized, and 14 received 40% total body surface area third-degree burn. IL-1alpha was administered intravenously at 1,000 ng/kg to seven pigs immediately after burn. Eighteen hours after burn, 100 microg/kg lipopolysaccharide (LPS) was administered intravenously. Systemic and splanchnic hemodynamics were measured and blood samples were drawn for blood gas analysis. Intestinal permeability was assessed every 6 hours by measuring the lactulose/mannitol (L/M) excretion ratio. At the end of the study (42 hours), tissue samples were harvested for bacteriologic cultures.


RESULTS
Mesenteric blood flow was significantly decreased after burn and endotoxin. Administration of IL-1alpha significantly improved mesenteric blood flow postburn and post-LPS. Mesenteric oxygen supply and consumption showed a significant reduction after burn. In contrast, animals treated with IL-1alpha showed an increase in postburn mesenteric oxygen supply and consumption. LPS-induced mesenteric hypoxia was also ameliorated by IL-1alpha treatment. Intestinal permeability, as assessed by the L/M ratio, showed a 7- and 10-fold elevation after thermal injury and LPS, respectively. In contrast, IL-1alpha-treated animals showed an increase of only three- and fourfold in the L/M ratio, respectively. Bacterial translocation was significantly increased in the burn/endotoxin group. IL-1alpha significantly reduced the rates of bacterial translocation.


CONCLUSIONS
IL-1alpha treatment attenuates mesenteric ischemia and reperfusion injury induced by thermal injury and endotoxemia by improving mesenteric blood flow and oxygenation. Subsequently, IL-1alpha reduces intestinal permeability and bacterial translocation after burn and sepsis.
Tadros
Tamer
T
Shriners Burns Institute, Galveston, Texas, USA. tadros@hlkd.azr.nl
Traber
Daniel L
DL
Heggers
John P
JP
Herndon
David N
DN
D000704:Analysis of Variance; D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects*; D002056:Burns / Q000150:complications / Q000188:drug therapy*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology*; D007410:Intestinal Diseases / Q000188:drug therapy*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology; D007511:Ischemia / Q000188:drug therapy*; D010101:Oxygen Consumption; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D015427:Reperfusion Injury / Q000188:drug therapy*; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000150:complications / Q000188:drug therapy*; D013152:Splanchnic Circulation / Q000187:drug effects; D013556:Swine, Miniature; D016896:Treatment Outcome
D007375:Interleukin-1