Objective: To study the therapeutic effects of human interleukin 10 (IL-10) gene transfer on severe acute pancreatitis (SAP) in rats.
Methods: Twenty healthy SD rats were injected intraperitoneally with SA liposome, SA liposome/pcDNA3 or SA liposome/pcDNA3-IL-10. Another twenty SD rats were randomly divided into five groups: rats in one group underwent laparotomy only (normal control), and SAP was induced in the other 4 groups induced by homogeneous injection of sodium taurocholate beneath the pancreatic capsule. Among the 4 SAP groups, one group did not receive any drugs, and liposomes, pcDNA3 or pcDNA3-IL-10 complexed with cationic liposomes were administered to the other groups. Drugs were administered by a single intraperitoneal injection thirty minutes after SAP had been induced. The levels of IL-10 in pancreas, liver and lungs were determined by ELISA kits. The level of serum amylase, histology, and tissue tumor necrosis factor (TNF) were assessed and mortality rate was observed in different groups for one week.
Results: The levels of IL-10 in the pancreas, liver and lung 24 hours after IL-10 gene transfer, increased significantly (all > 350 pg/g), and then gradually decreased, however, the levels of IL-10 were still significantly higher that those in the control groups (P < 0.05) 96 hours later and decreased to normal in one week. The levels of IL-10 of transfer control group were not significantly different from those of the normal control group. The levels of IL-10 expression in pancreas, liver and lungs were increased significantly in the gene therapy group, compared with the SAP group. The serum amylase level was (4 300 +/- 700) U/L in normal control group, increased to (20 300 +/- 1 100) U/L 24 hour after SAP induction without a difference between the therapy control group and SAP group, and decreased to (6 800 +/- 700) U/L after IL-10 gene therapy (P < 0.05). The histological score of pancreas was 4.1 +/- 0.2 24 hours after the induction of SAP, and was 3.2 +/- 0.3 in the IL-10 therapy group. The level of TNF in pancreas, liver, and lungs 24 hours after the induction of SAP was significantly higher than that in normal control group (P < 0.05) and was not different from that in therapeutic control group. However, it was decreased markedly in IL-10 therapy group (P < 0.05). No rat in any group died within 2 days after onset. There was no difference of mortality between SAP group and therapeutic control group. The one-week mortality was 90% in the whole SAP group. The one-week mortality of IL-10 gene therapy group was 30 %, significantly lower than that in SAP group (P < 0.05). There was no significant difference in the therapeutic control groups and the SAP group. The values of relative risk of SAP group, SA liposome group, and pcDNA3 group were 12, 8, and 11 times higher than that of gene therapy group (P < 0.05).
Conclusion: Cationic liposome mediated pcDNA3-IL-10 gene therapy decreases significantly the severity and mortality of SAP.