Beneficial effects of pentoxifylline treatment of experimental acute pancreatitis in rats.

Abstract

Unlabelled: The purposes of this study were to determine the tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels after the induction of acute necrotizing pancreatitis, and to establish the effects of pentoxifylline on cytokine production.

Methods: acute pancreatitis was induced by the retrograde injection of 200 microliters taurocholic acid into the pancreatic duct in male Wistar rats. The serum amylase activity, the wet pancreatic weight/body weight ratio, and the TNF and IL-6 levels were measured. Seven mg/kg pentoxifylline were administered intraperitoneally at the time of operation 6, 12 or 24 h later. Rats were killed 6, 24, 48 or 72 h after the operation.

Results: the TNF bioassay revealed high levels of TNF (30.2 +/- 5.4 U/ml, 35.0 +/- 5.0 U/ml and 36.6 +/- 6.0 U/ml) in the control group at 6, 24 and 48 h and (54.1 +/- 20 U/ml and 10.9 +/- 4.2 U/ml) in the pentoxifylline-treated group at 6 and 24 h, respectively, whereas the level had decreased to zero in the pentoxifylline-treated group at 48 h. The IL-6 bioassay likewise demonstrated high levels of IL-6 in the control group at 48 h and in the pentoxifylline-treated group at 6 and 24 h, and markedly decreased levels in the pentoxifylline-treated group at 48 h (7083 +/- 2844 pg/ml, 6463 +/- 1307 pg/ml, 10,329 +/- 5571 pg/ml vs 137.5 +/- 85.5 pg/ml, respectively, P < 0.05). The high mortality observed in the pancreatitis group (43%) was decreased by pentoxifylline administration to 11%.

Conclusion: these results demonstrate that pentoxifylline very effectively inhibits cytokine production in acute pancreatitis.