Time-course changes in serum cytokine levels in two experimental acute pancreatitis models in rats

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Abstract

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-α) 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-α 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 103 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-α 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 2h (43.2 ± 13 x 103 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-α 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-α may participate in the pathogenesis of these types of acute pancreatitis.

Original languageEnglish
Pages (from-to)153-161
Number of pages9
JournalResearch In Experimental Medicine
Volume196
Issue number3
DOIs
Publication statusPublished - Sep 5 1996

Keywords

  • Experimental acute pancreatitis
  • Interleukin 6
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Medicine(all)

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