Time-course changes in serum cytokine levels in two experimental acute pancreatitis models in rats.
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.
Takács
T
T
First Department of Medicine, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Farkas
G
G
Czakó
L
L
Jármay
K
K
Mándi
Y
Y
Lonovics
J
J
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001835:Body Weight; D002779:Cholestasis / Q000097:blood / Q000601:surgery; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000097:blood*; D007813:Laparotomy; D008026:Ligation; D008297:Male; D009929:Organ Size; D010195:Pancreatitis / Q000097:blood* / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000009:adverse effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000681:Amylases; D012844:Sincalide