Microvascular effects of oral interleukin-6 on ischemia/reperfusion in the murine small intestine.
Oral administration of interleukin-6 (IL-6) has been shown to reduce hemorrhage-induced bacterial translocation from the gut in mice and rats. To examine the intestinal microvasculature, mice were given the electron-dense tracer horseradish peroxidase (HRP) after hemorrhage and IL-6 or vehicle administration. In normal mice and in those hemorrhaged and given IL-6, the electron-dense marker, administered intravenously, could be found in intestinal capillaries and between mucosal epithelial cells, suggesting that the microvasculature was patent. In mice given saline after shock, however, no marker was present in the gut, suggesting that the intestinal microvasculature was unable to deliver the marker to the epithelia. When mice were given HRP intralumenally (il) the tracer was able to penetrate between intestinal epithelial cells only in mice given vehicle after hemorrhage. This finding suggests that hemorrhaged mice were susceptible to sepsis and endotoxic shock from the leaky gut. In normal and IL-6-treated mice, the tracer was unable to pass from the lumen between mucosal epithelial cells, because the presence of an intact zonula occludens prevented passage. Functional studies supported the electron microscopy findings. Bacteria were cultured from the livers of mice fed vehicle after hemorrhage, but not from those fed IL-6. These data support the conclusions that parts of the intestinal microvasculature remain diminished after hemorrhage and resuscitation and that oral IL-6 restores this circulation.
Rollwagen
F M
FM
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA. frollag@usuhs.mil
Li
Y Y
YY
Pacheco
N D
ND
Dick
E J
EJ
Kang
Y H
YH
D000284:Administration, Oral; D000818:Animals; D001419:Bacteria / Q000302:isolation & purification; D005260:Female; D006470:Hemorrhage / Q000503:physiopathology; D006735:Horseradish Peroxidase / Q000008:administration & dosage / Q000493:pharmacokinetics; D007082:Ileum; D007267:Injections; D015850:Interleukin-6 / Q000494:pharmacology*; D007421:Intestine, Small / Q000098:blood supply*; D007422:Intestines / Q000098:blood supply; D007511:Ischemia / Q000473:pathology*; D008099:Liver / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000187:drug effects*; D008854:Microscopy, Electron; D011994:Recombinant Proteins / Q000494:pharmacology; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000473:pathology*
D015850:Interleukin-6; D011994:Recombinant Proteins; D006735:Horseradish Peroxidase