Abstracts
1997 Digestive Disease Week

Cationic liposome-mediated gene transfer during acute pancreatitis: tissue specificity, duration, and effects of acute inflammation.

W Denham, J Yang, G Carter, C Tannahill, S Mackay, A Rosemurgy, L Moldawer, J Norman. Departments of Surgery, University of South Florida, Tampa, FL and University of Florida, Gainesville, FL.

Introduction. Production of inflammatory cytokines in the pancreas, lung, and liver are believed to play a major role in the development of severe pancreatitis. This tissue-specific production could lend itself to directed anti-cytokine gene therapy if an appropriate delivery system could be developed. This study was undertaken to examine a novel approach for the delivery of protein-based therapies to the tissues involved during acute pancreatitis.

Methods. Healthy mice received intraperitoneal injection of cationic liposomes and a DNA plasmid containing the chloramphenicol acetyl transferase (CAT) reporter gene. Twelve mice were sacrificed at 24 hours and their serum, pancreas, lungs, and liver harvested. To determine the effect of tissue inflammation on gene transfer efficiency, acute pancreatitis was induced (caerulein, 50 µg/kg/hr IP x 4) in additional mice concurrent with CAT transfection. The presence of pancreatitis was established in all animals by histologic scoring of pancreata and by serum amylase and lipase. CAT transfection efficiency was determined by colormetric assay of tissue homogenates.

Results. All animals which received the liposome were successfully transfected with the CAT gene into the pancreas (133 ± 14 mEU/mg protein), lungs (47 ± 5), and liver (36 ± 4), [data = mean ± SEM, all p<0.0001 vs control (0.018 ±.001)]. No healthy animals receiving the CAT gene developed elevations in amylase, lipase, or any of the histologic parameters of pancreatitis (all p=ns). Transfection efficiency in each organ was not affected by pre-existing pancreatitis (p=ns) and was not altered with delayed induction of pancreatitis (p=ns).

Conclusions. Gene transfection into the pancreas, liver, and lungs is possible using a cationic liposome delivery system which does not induce pancreatitis or pancreatic inflammation. Pancreatic expression of the gene product is equal to or greater than the organs of the reticuloendothelial system and continues at or above 100% efficiency during acute pancreatitis.