Intereukin-10 and kupffer cells protect steatotic mice livers from ischemia-reperfusion injury

Alton G. Sutter, Arun P. Palanisamy, Justin D. Ellet, Michael G. Schmidt, Rick G. Schnellmann, Kenneth D. Chavin

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Steatotic livers are more sensitive to ischemia/reperfusion (I/R) and are thus routinely rejected for transplantation because of their increased rate of primary nonfunction (PNF). Lean livers have less I/R-induced damage and inflammation due toKupffer cells (KC), which are protective after total, warm, hepatic I/R with associated bowel congestion. This protection has been linked to KC-dependent expression of the potent anti-inflammatory cytokine interleukin-10 (IL-10).We hypothesized that pretreatment with exogenous IL-10would protect the steatotic livers of genetically obese (ob/ob) mice from inflammation and injury induced by I/R. Lean and ob/ob mice were pretreated with either IL-10 or liposomally-encapsulated bisphosphonate clodronate (shown to deplete KC) prior to total, warm, hepatic I/R. IL-10 pretreatment increased survival of ob/ob animals at 24 hrs post-I/R from 30% to 100%, and significantly decreased serum ALT levels. At six hrs post-I/R, IL-10 pretreatment increased IL-10 mRNA expression, but suppressed up-regulation of the pro-inflammatory cytokine IL-1_ mRNA. However, ALT levels were elevated at six hrs post-I/R in KC-depleted animals. These data reveal that pretreatment with IL-10 protects steatotic livers undergoing I/R, and that phagocytically active KC retain a hepatoprotective role in the steatotic environment.

Original languageEnglish (US)
Pages (from-to)69-76
Number of pages8
JournalEuropean cytokine network
Volume25
Issue number4
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

Keywords

  • Cytokine
  • IL10
  • Inflammation
  • Liver
  • Obesity
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry

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