@Article{ecn.2015.0359,
AUTHOR = {Alton G. Sutter, Arun P. Palanisamy, Justin D. Ellet, Michael G. Schmidt, Rick G. Schnellmann, Kenneth D. Chavin},
TITLE = {Intereukin-10 and Kupffer cells protect steatotic mice livers from ischemia-reperfusion injury},
JOURNAL = {European Cytokine Network},
VOLUME = {25},
YEAR = {2014},
NUMBER = {4},
PAGES = {69--76},
URL = {http://www.techscience.com/ECN/v25n4/65555},
ISSN = {1952-4005},
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.},
DOI = {10.1684/ecn.2015.0359}
}