Interleukin-11 protects mouse liver from warm ischemia/reperfusion (WI/Rp) injury

Clin Res Hepatol Gastroenterol. 2016 Nov;40(5):562-570. doi: 10.1016/j.clinre.2015.11.009. Epub 2016 Mar 23.

Abstract

Background: IL-11 is a multifunctional cytokine that belongs to the IL-6 family. Previous studies have demonstrated that IL-11 has underlying anti-inflammatory and anti-apoptotic properties. In this study, we evaluated the potential effects of IL-11 on mouse liver WI/Rp injury.

Methods: For in vivo experiments, mice were randomly divided into four main experimental groups (n=5 each): (1) normal group - anesthesia; (2) sham group- laparotomy; (3) I/R group- liver WI/Rp; and (4) IL-11 pretreatment (500μg/kg, tail vein injection) group- administration of RhIL-11 2h before liver WI/Rp induced in the same manner as in group 3. For in vitro experiments, cells were divided into two groups: (1) H/R group- H/R; and (2) IL-11 pretreatment group- pretreatment with RhIL-11 (2μg/mL for 12h) before the induction of H/R. For both groups, three periods of reoxygenation were examined (2h, 6h, and 12h).

Results: In the in vivo experiments, IL-11 protected mouse livers from WI/Rp by reducing liver enzyme levels and cellular degeneration. In the in vitro experiments, IL-11 significantly reduced hepatocyte apoptosis. In both the in vivo and in vitro experiments, IL-11 pre-treatment significantly reduced the expression of TNF-α and IL-1β. In addition, NF-κB, a target of IL-11, was suppressed in macrophages after IL-11 pre-treatment.

Conclusions: Pre-treatment with IL-11 protects mouse livers from WI/Rp injury by suppressing NF-kB activity.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Apoptosis / drug effects
  • Aspartate Aminotransferases / blood
  • Cells, Cultured
  • Hepatocytes / pathology
  • Interleukin-11 / pharmacology*
  • Interleukin-1beta / metabolism
  • Liver / blood supply*
  • Liver / metabolism
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Random Allocation
  • Reperfusion Injury / prevention & control*
  • Tumor Necrosis Factor-alpha / metabolism
  • Warm Ischemia*

Substances

  • Interleukin-11
  • Interleukin-1beta
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Aspartate Aminotransferases
  • Alanine Transaminase