title: Reduced severity of liver ischemia/reperfusion injury following hepatic resection in humans is associated with enhanced intrahepatic expression of Th2 cytokines.
abstract: BACKGROUND
  Based on previous studies in experimental models, pro-inflammatory Th1 cytokines (i.e. TNF-alpha and IFN-gamma) are thought to play a pathogenic role in hepatic ischemia/reperfusion injury, while anti-inflammatory Th2 cytokines (i.e. IL-4 and IL-10) have been associated with reduced liver disease severity. To test the relevance of these concepts in humans, cytokine expression profiles were characterized in liver biopsies from patients undergoing hepatic resection following intermittent portal clamping.
  
  
  METHODS
  Twelve patients were analyzed for the intrahepatic expression of TNF-alpha, IFN-gamma, IL-4 and IL-10 before and about 90min after the last reperfusion. In addition, parameters of liver damage including sALT and serum levels of TNF-alpha were analyzed at 2, 24 and 48h after surgery.
  
  
  RESULTS
  When compared with pre-reperfusion liver specimens, all post-reperfusion biopsies showed significantly increased levels of TNF-alpha and IFN-gamma mRNAs. Conversely IL-4 and IL-10 mRNA levels were significantly increased in only seven patients. A negative correlation was observed between Th2 cytokines (IL-4, IL-10) and ALT and serum levels of TNF-alpha. Furthermore, the presence of hepatic steatosis was significantly associated with lower intrahepatic contents of IL-4 and IL-10.
  
  
  CONCLUSIONS
  The results suggest that the local early expression of Th2 cytokines may contribute to attenuate liver injury following ischemia reperfusion in humans. The early imbalance between pro- and anti-inflammatory cytokines seen in steatotic liver subjected to I/R could explain, at least partially, the decreased tolerance of steatotic livers to I/R injury.
authors.affiliation: Department of Surgery, Liver Unit, Scientific Institute San Raffaele, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pulitanò
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sitia
authors.forename: Luca
authors.initials: L
authors.lastname: Aldrighetti
authors.forename: Renato
authors.initials: R
authors.lastname: Finazzi
authors.forename: Marcella
authors.initials: M
authors.lastname: Arru
authors.forename: Marco
authors.initials: M
authors.lastname: Catena
authors.forename: Luca G
authors.initials: LG
authors.lastname: Guidotti
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Ferla