title: Intereukin-10 and Kupffer cells protect steatotic mice livers from ischemia-reperfusion injury.
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.
authors: Division of Transplant Surgery, Department Of Surgery.
authors: Alton G
authors: AG
authors: Sutter
authors: Division of Transplant Surgery, Department Of Surgery.
authors: Arun P
authors: AP
authors: Palanisamy
authors: Division of Transplant Surgery, Department Of Surgery.
authors: Justin D
authors: JD
authors: Ellet
authors: Department of Microbiology and Immunology.
authors: Michael G
authors: MG
authors: Schmidt
authors: Department of Drug Discovery and Biomedical Sciences, Medical University Of South Carolina, Charleston, SC, USA, and, R.H. Johnson Veterans Administration Medical Center, Charleston, SC, USA.
authors: Rick G
authors: RG
authors: Schnellmann
authors: Division of Transplant Surgery, Department Of Surgery.
authors: Kenneth D
authors: KD
authors: Chavin
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000276:immunology; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D004002:Clodronic Acid / Q000494:pharmacology; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D015870:Gene Expression; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: D050071:Bone Density Conservation Agents; C556062:IL10 protein, mouse; D053583:Interleukin-1beta; D012333:RNA, Messenger; D004002:Clodronic Acid; D016753:Interleukin-10; D000410:Alanine Transaminase
keywords: IL10; cytokine; inflammation; liver; obesity; transplantation