Mole Damian J, McFerran Neil V, Diamond Thomas
Clinical and Surgical Sciences (Surgery), University of Edinburgh, Edinburgh, UK.
Pancreatology. 2008;8(4-5):478-87. doi: 10.1159/000151775. Epub 2008 Sep 3.
Altered lipopolysaccharide (LPS)-responsiveness is a key feature of acute pancreatitis (AP)-associated multiple organ failure (AP-MOF) in rats and humans.
To determine the differential expression of 16 cytokines and chemokines in response to delayed LPS administration in established experimental AP-MOF in rats.
In a cubic factorial group design (12 groups, n = 6 rats/group), 0, 6 and 30 microg/kg Escherichia coli 0111:B4 LPS was administered intra-arterially, 18 h into experimental AP-MOF or sham laparotomy. AP was induced by intraductal glycodeoxycholic acid and intravenous caerulein. Central venous serum concentrations of 16 cytokines and chemokines were measured by Searchlight multiplex ELISA.
Four patterns were observed: (1) TNF-alpha, IL-1alpha, IL-1beta, IL-6, IFN-gamma, MCP-1, MIP-2alpha, MIP-3alpha, fractalkine and RANTES showed a diminished LPS response in AP versus sham (p < 0.001, ANOVA); (2) IL-2, IL-4 and GM-CSF levels were undetectable; (3) CINC-2alpha and GRO/KC showed little or no difference between AP and controls, and (4) IL-10 concentrations after 0 and 6 microg/kg, but not 30 microg/kg LPS injection were significantly higher in AP than controls (p < 0.001, ANOVA).
Experimental AP-MOF in rats results in differential preservation of the cytokine and chemokine response to LPS challenge, with a predominantly regulatory expressed phenotype.
脂多糖（LPS）反应性改变是大鼠和人类急性胰腺炎（AP）相关多器官功能衰竭（AP-MOF）的关键特征。
确定在已建立的大鼠实验性AP-MOF中，延迟给予LPS后16种细胞因子和趋化因子的差异表达。
采用立方析因组设计（12组，每组n = 6只大鼠），在实验性AP-MOF或假手术18小时后，经动脉给予0、6和30微克/千克大肠杆菌0111:B4 LPS。通过导管内甘氨脱氧胆酸和静脉注射蛙皮素诱导AP。采用Searchlight多重ELISA法测定中心静脉血清中16种细胞因子和趋化因子的浓度。
观察到四种模式：（1）与假手术组相比，AP组中肿瘤坏死因子-α、白细胞介素-1α、白细胞介素-1β、白细胞介素-6、干扰素-γ、单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-2α、巨噬细胞炎性蛋白-3α、 fractalkine和调节激活正常T细胞表达和分泌因子（RANTES）的LPS反应减弱（p < 0.001，方差分析）；（2）白细胞介素-2、白细胞介素-4和粒细胞-巨噬细胞集落刺激因子水平未检测到；（3）细胞因子诱导中性粒细胞趋化因子-2α（CINC-2α）和生长调节致癌基因蛋白/角质形成细胞趋化因子（GRO/KC）在AP组和对照组之间几乎没有差异，（4）在注射0和6微克/千克LPS后，但不是30微克/千克LPS后，AP组白细胞介素-10浓度显著高于对照组（p < 0.001，方差分析）。
大鼠实验性AP-MOF导致细胞因子和趋化因子对LPS刺激的反应存在差异，主要表现为调节性表达表型。
