Intestinal permeability is reduced and IL-10 levels are increased in septic IL-6 knockout mice.
Sepsis is associated with increased intestinal permeability, but mediators and mechanisms are not fully understood. We examined the role of interleukin (IL)-6 and IL-10 in sepsis-induced increase in intestinal permeability. Intestinal permeability was measured in IL-6 knockout (IL-6 -/-) and wild-type (IL-6 +/+) mice 16 h after induction of sepsis by cecal ligation and puncture or sham operation. In other experiments, mice or intestinal segments incubated in Ussing chambers were treated with IL-6 or IL-10. Intestinal permeability was assessed by determining the transmucosal transport of the 4.4-kDa marker fluorescein isothiocyanate conjugated dextran and the 40-kDa horseradish peroxidase. Intestinal permeability for both markers was increased in septic IL-6 +/+ mice but not in septic IL-6 -/- mice. Treatment of nonseptic mice or of intestinal segments in Ussing chambers with IL-6 did not influence intestinal permeability. Plasma IL-10 levels were increased in septic IL-6 -/- mice, and treatment of septic mice with IL-10 resulted in reduced intestinal permeability. Increased intestinal permeability during sepsis may be regulated by an interaction between IL-6 and IL-10. Treatment with IL-10 may prevent the increase in mucosal permeability during sepsis.
Wang
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Department of Surgery, the Shriners Hospitals for Children, Cincinnati, Ohio 45267-0558, USA.
Fang
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CH
Hasselgren
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PO
D000818:Animals; D001202:Ascitic Fluid / Q000382:microbiology; D002432:Cecum / Q000382:microbiology / Q000473:pathology; D015169:Colony Count, Microbial; D003911:Dextrans / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008026:Ligation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010477:Perfusion; D010539:Permeability / Q000187:drug effects*; D018805:Sepsis / Q000503:physiopathology*; D015996:Survival Rate
D003911:Dextrans; D015850:Interleukin-6; C015219:fluorescein isothiocyanate dextran; D006735:Horseradish Peroxidase; D016650:Fluorescein-5-isothiocyanate