Department of Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.
Chin Med J (Engl). 2013;126(10):1855-9.
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.
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-α) levels were measured.
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.
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.
白细胞介素（IL）-33 是最近发现的 IL-1 家族成员，它与受体 ST2L 结合。本研究检测了小鼠肝脏中 IL-33 的产生，并研究了其在肝缺血/再灌注（I/R）损伤中的作用。
雄性 BALB/c 小鼠（（22 ± 3）g）接受 90 分钟部分肝缺血，然后再灌注 6 小时。首先，将小鼠随机分为两组：对照组（仅剖腹术，不阻断血供）和缺血模型组。在缺血后 30、60、90 分钟及再灌注后 2、6 小时测量 IL-33 mRNA 和血清蛋白水平。其次，将小鼠随机分为四组：对照组、模型组（注射兔 IgG 多克隆抗体）、重组 IL-33 干预组和抗 ST2L 抗体干预组。再灌注 6 小时后处死小鼠。通过透射电镜观察肝组织病理学变化。测量血清天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、IL-4、IL-5、IL-13、干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）水平。
IL-33 mRNA 和蛋白在缺血过程中没有变化（P > 0.05），但在再灌注过程中显著增加（P < 0.05）。再灌注 6 小时后，血清 ALT、AST、IL-4、IL-5、IL-13、IFN-γ和 TNF-α水平明显升高（P < 0.05），肝细胞超微结构受损。与对照组相比，IL-33 预处理减轻了肝损伤的严重程度，但抗 ST2L 抗体预处理则增加了损伤的严重程度。IL-33 预处理后，血清 IL-4、IL-5 和 IL-13 蛋白水平升高，IFN-γ 水平降低。与对照组相比，抗 ST2L 抗体预处理显著降低了血清 IL-4、IL-5、IL-13 水平，升高了血清 IFN-γ 水平（P < 0.05）。TNF-α 水平无变化。
IL-33 在 I/R 损伤过程中在肝脏中系统地和局部产生。IL-33 预处理对肝 I/R 损伤具有治疗作用，可能通过诱导 Th1 向 Th2 转变。
