Antisense gene therapy in thermally injured mice orally infected with Enterococcus faecalis (44.27)

Abstract

Abstract Infectious complications stemming from E. faecalis translocation in burn mice are influenced by a special subset of neutrophils (immunosuppressive PMN, PMN-II). CCL2 released from PMN-II has been characterized as an effector molecule when translocated bacteria spread systemically in these mice. In the present study, we tried to protect burn mice orally infected with E. faecalis using antisense gene therapy. c-fos antisense ODN was utilized in this gene therapy, because c-fos was described as a promoter of CCL2 gene expression. One day after burn injury (3rd degree, 25% TBSA burn), decontaminated BALB/c mice were infected orally with a lethal dose of E. faecalis (107 CFU/mouse), and treated s.c. with c-fos antisense ODN 6 hrs before, and 2 and 4 days after infection. These mice were observed once daily for a week, to determine their survival rates. In some experiments, sera obtained from burn mice, that were treated with or without c-fos antisense ODN, were assayed for CCL2 using ELISA. In the results, after E. faecalis oral infection, 90% of burn mice subjected to antisense therapy survived, while an 80% mortality rate was shown in the same mice treated with c-fos sense ODN. CCL2 was not detected in sera of burn mice treated with c-fos antisense ODN. These results indicate that infectious complications caused by E. faecalis translocation are controllable in thermally injured mice by antisense gene therapy using c-fos antisense ODN. This study was supported by SHC NA #8840.