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Intereukin-10 and Kupffer cells protect steatotic mice livers from ischemia-reperfusion injury
| Content Provider | PubMed Central |
|---|---|
| Author | Sutter, Alton G. Palanisamy, Arun P. Ellet, Justin D. Schmidt, Michael G. Schnellmann, Rick G. Chavin, Kenneth D. |
| 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. |
| Related Links | http://dx.doi.org/10.1684/ecn.2015.0359 |
| Starting Page | 69 |
| File Format | |
| ISSN | 19524005 |
| e-ISSN | 19524005 |
| Journal | European cytokine network |
| Issue Number | 4 |
| Volume Number | 25 |
| Language | English |
| Publisher Date | 2014-01-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Clinical Biochemistry Immunology |
