Plasma levels of TNF and IL-6 following induction of acute pancreatitis and pentoxifylline treatment in rats

Activation of cytokine cascade is a decisive factor in determining the pathobiology of different inflammatory processes including acute pancreatitis. The purposes of this study were to determine the TNF and IL-6 levels after the induction of acute necrotizing pancreatitis, and to establish the effects of pentoxifylline on the cytokine production and the severity of pancreatitis. Acute necrotizing pancreatitis was induced by the retrograde injection of 200 microliters taurocholic acid into the pancreatic duct in male Wistar rats. TNF was titrated in a bioassay on cell line WEHI clone 164. IL-6 was measured via its proliferative action on the IL-6 dependent mouse hybridoma cell line B-9. Seven mg/kg pentoxifylline was administered intraperitoneally at the time of operation and/or 24 hours later. Rats were sacrificed, 48 or 72 hours after the operation. The TNF bioassay revealed high levels of TNF (36.6 +/- 6.0 U/ml) in the control group whereas levels decreased to zero in the pentoxifylline-treated group. The IL-6 bioassay likewise demonstrated high levels of IL-6 in the control group and markedly decreased levels in the pentoxifylline treated group (7083 +/- 2844 pg/ml, 6463 +/- 1307 pg/ml vs. 137.5 +/- 85.5 pg/ml, respectively, p < 0.05). The high mortality observed in the control group (43%) was sharply decreased by pentoxifylline administration to 11%. The data suggest that pentoxifylline is capable of modifying the cytokine production after 48 hours of induction of acute pancreatitis.