Open Access

ARTICLE

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

Alton G. Sutter¹, Arun P. Palanisamy¹, Justin D. Ellet¹, Michael G. Schmidt², Rick G. Schnellmann^3,4, Kenneth D. Chavin¹

1 Division of Transplant Surgery, Department Of Surgery
2 Department of Microbiology and Immunology
3 Department of Drug Discovery and Biomedical Sciences, Medical University Of South Carolina, Charleston, SC, USA
4 R.H. Johnson Veterans Administration Medical Center, Charleston, SC, USA

* Corresponding Author: Kenneth D Chavin,

European Cytokine Network 2014, 25(4), 69-76. https://doi.org/10.1684/ecn.2015.0359

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 to Kupffer 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-10 would 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-1β 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.

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