Pretreatment with interleukin-33 reduces warm hepatic ischemia/reperfusion injury in mice |
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Authors: | LI Shu ZHU Feng-xue ZHANG Hong-bin LI Hui and AN You-zhong |
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Institution: | Department of Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China |
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Abstract: | Background Interleukin (IL)-33 is a recently identified member of the IL-1 family that binds to the receptor,ST2L.This study examined IL-33 production in mouse liver and investigated its role in hepatic ischemia/reperfusion (I/R) injury.Methods Male BALB/c mice ((22±3) g) were subjected to 90 minutes partial hepatic ischemia,followed by 6 hours reperfusion.First,mice were randomized into two groups:control group (laparotomy only,without blocking blood supply) and ischemia model group.IL-33 mRNA and serum protein levels were measured at 30,60,90 minutes after ischemia and 2 and 6 hours after reperfusion.Second,mice were randomized into four groups:control,model (injection of rabbit IgG polyclonal antibody),recombinant IL-33 intervention and anti-ST2L antibody intervention group.Mice were sacrificed 6 hours after reperfusion.Liver pathology was observed via transmission electron microscopy.Serum aspartate aminotransferase (AST),alanine aminotransferase (ALT),IL-4,IL-5,IL-13,interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-a) levels were measured.Results Levels of IL-33 mRNA and protein did not change during ischemia (P >0.05) but increased significantly during reperfusion (P <0.05).After reperfusion for 6 hours,serum levels of ALT,AST,IL-4,IL-5,IL-13,IFN-γ and TNF-α were significantly increased (P <0.05),and hepatocellular ultrastructure was damaged.Pretreatment with IL-33 attenuated severity of liver damage compared with controls,but pretreatment with anti-ST2L antibody increased severity.Serum levels of IL-4,IL-5 and IL-13 protein increased whereas IFN-γ decreased following IL-33 pretreatment.Pretreatment with anti-ST2L antibody significantly decreased serum IL-4,IL-5,IL-13 levels and increased serum IFN-γ levels compared with controls (P <0.05).There was no change in the level of TNF-α.Conclusion IL-33 is produced systematically and locally in liver during I/R injury.Pretreatment with IL-33 is therapeutic for hepatic I/R injury,possibly via inducing a Th1 to Th2 shift. |
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Keywords: | liver ischemia/reperfusion T helper lymphocyte interleukin-33 |
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