TIME-COURSE CHANGES IN SERUM CYTOKINE LEVELS IN 2 EXPERIMENTAL ACUTE-PANCREATITIS MODELS IN RATS

Activated leukocytes and cytokines have important roles in the multisy stem involvement during acute pancreatitis. The changes in the serum l evel of tumor necrosis factor-alpha (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 overdo se of cholecystokinin octapeptide (CCK-8), while a severe hemorrhagic form of pancreatitis was induced by ligation of the common bilio-pancr eatic duct. The rats were examined 2, 4, 8, 16, 24 and 48 h after panc reatitis induction. The severity of the inflammation was assessed by m easurement of the serum amylase activity, quantification of the edema, and histological examination. Serum TNF-alpha and IL-6 were determine d 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 si gnificantly elevated at 2 h, and the maximum levels were observed at 4 h (8.19+/-1.13 mg/g and 69.4+/-12.8x10(3) U/ml, respectively). Both p arameters subsequently decreased continuously during the observation p eriod. The serum IL-6 level was significantly increased at 4 h relativ e 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 r atio pw/bw increased continuously during the study and reached the max imum 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 a t 2 h (43.2+/-13x10(3) U/ml), but then decreased continuously. The ser um 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 an d 24 h after pancreatitis induction. The results led to correlations b etween the serum IL-6 levels and the biochemical and morphological sev erity of acute pancreatitis in both experimental models. The data sugg est that IL-6 and TNF-alpha may participate in the pathogenesis of the se types of acute pancreatitis.