Intestinal permeability is reduced and IL-10 levels are increased in septic IL-6 knockout mice

Am J Physiol Regul Integr Comp Physiol. 2001 Sep;281(3):R1013-23. doi: 10.1152/ajpregu.2001.281.3.R1013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Ascitic Fluid / microbiology
  • Cecum / microbiology
  • Cecum / pathology
  • Colony Count, Microbial
  • Dextrans / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Fluorescein-5-isothiocyanate / analogs & derivatives
  • Fluorescein-5-isothiocyanate / metabolism
  • Horseradish Peroxidase / metabolism
  • Ileum / drug effects
  • Ileum / physiopathology
  • In Vitro Techniques
  • Injections, Intraperitoneal
  • Interleukin-6 / administration & dosage
  • Interleukin-6 / blood
  • Interleukin-6 / deficiency*
  • Intestinal Absorption*
  • Intestinal Mucosa / metabolism
  • Ligation
  • Male
  • Mice
  • Mice, Knockout
  • Perfusion
  • Permeability / drug effects*
  • Sepsis / physiopathology*
  • Survival Rate

Substances

  • Dextrans
  • Interleukin-6
  • fluorescein isothiocyanate dextran
  • Horseradish Peroxidase
  • Fluorescein-5-isothiocyanate