Takács T, Farkas G, Czakó L, Jármay K, Mándi Y, Lonovics J
First Department of Medicine, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Res Exp Med (Berl). 1996;196(3):153-61. doi: 10.1007/BF02576837.
Activated leukocytes and cytokines have important roles in the multi-system involvement during acute pancreatitis. The changes in the serum level of tumor necrosis factor-a (TNF-alpha) and interleukin-6 (IL-6) over time were investigated in two experimental acute pancreatitis models in rats. Mild edematous pancreatitis was induced with an overdose of cholecystokinin octapeptide (CCK-8), while a severe hemorrhagic form of pancreatitis was induced by ligation of the common bilio-pancreatic duct. The rats were examined 2, 4, 8, 16, 24 and 48 h after pancreatitis induction. The severity of the inflammation was assessed by measurement of the serum amylase activity, quantification of the edema, and histological examination. Serum TNF-alpha and IL-6 were determined by bioassay, using the TNF-sensitive WEHI 164 and the IL-6-dependent B9 cell lines, respectively. In CCK-8-induced acute pancreatitis, the pancreatic weight/body weight ratio (pw/bw) and amylase level were significantly elevated at 2 h, and the maximum levels were observed at 4 h (8.19 +/- 1.13 mg/g and 69.4 +/- 12.8 x 10(3) U/ml, respectively). Both parameters subsequently decreased continuously during the observation period. The serum IL-6 level was significantly increased at 4 h relative to the controls (123.3 +/- 5.8 vs 37.5 +/- 15 pg/ml), and then decreased continuously. In this model, only a moderate level of serum TNF-alpha was observed at 2 h. In the biliary type of acute pancreatitis, the ratio pw/bw increased continuously during the study and reached the maximum level at 48 h relative to the sham-operated control (8.8 +/- 1.4 vs 5.3 +/- 0.8 mg/g). The serum amylase level was significantly elevated at 2 h (43.2 +/- 13 x 10(3) U/ml), but then decreased continuously. The serum IL-6 reached its maximum level at 16 h (3800 +/- 447 pg/ml). In this model, increased TNF-alpha levels (75-300 U/ml) were measured 8, 16 and 24 h after pancreatitis induction. The results led to correlations between the serum IL-6 levels and the biochemical and morphological severity of acute pancreatitis in both experimental models. The data suggest that IL-6 and TNF-alpha may participate in the pathogenesis of these types of acute pancreatitis.
活化的白细胞和细胞因子在急性胰腺炎多系统受累过程中发挥重要作用。在两种大鼠实验性急性胰腺炎模型中，研究了肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）血清水平随时间的变化。过量注射八肽胆囊收缩素（CCK-8）诱导轻度水肿性胰腺炎，而结扎胆总管诱导严重出血性胰腺炎。在胰腺炎诱导后2、4、8、16、24和48小时对大鼠进行检查。通过测量血清淀粉酶活性、定量水肿和组织学检查评估炎症的严重程度。分别使用对TNF敏感的WEHI 164细胞系和依赖IL-6的B9细胞系，通过生物测定法测定血清TNF-α和IL-6。在CCK-8诱导的急性胰腺炎中，胰腺重量/体重比（pw/bw）和淀粉酶水平在2小时时显著升高，在4小时时达到最高水平（分别为8.19±1.13mg/g和69.4±12.8×10³U/ml）。在观察期内，这两个参数随后持续下降。血清IL-6水平在4小时时相对于对照组显著升高（123.3±5.8对37.5±15pg/ml），然后持续下降。在该模型中，在2小时时仅观察到中等水平的血清TNF-α。在胆源性急性胰腺炎中，pw/bw比值在研究过程中持续增加，相对于假手术对照组，在48小时时达到最高水平（8.8±1.4对5.3±0.8mg/g）。血清淀粉酶水平在2小时时显著升高（43.2±13×10³U/ml），但随后持续下降。血清IL-6在16小时时达到最高水平（3800±447pg/ml）。在该模型中，在胰腺炎诱导后8、16和24小时测量到TNF-α水平升高（75 - 300U/ml）。结果表明，在两种实验模型中，血清IL-6水平与急性胰腺炎的生化和形态学严重程度之间存在相关性。数据表明，IL-6和TNF-α可能参与了这些类型急性胰腺炎的发病机制。
