Resistance of subacutely burned mice (SAB-mice) therapeutically treated with CCL1 antisense ODN against infections with MRSA or enterococci (INC4P.344)

Abstract

Abstract In previous studies, sepsis stemming for E. faecalis translocation and MRSA local infection has been greatly controlled in SAB-mice prophylactically treated with CCL1 antisense ODN. Effector cells (M1Mφ) in host antibacterial immunities are isolated from the infected SAB-mice after treatment with the ODN. In this study, the antibacterial resistance of SAB-mice therapeutically treated with the ODN was examined against infections with E. faecalis and MRSA. Mice 2 weeks after flame burn injury (3rd degree 25% TBSA) were infected with MRSA (106 CFU/mouse, i.v.). Decontaminated mice 2 weeks after burn injury were infected with E. faecalis (8 x 106 CFU/mouse, p.o.). These mice were therapeutically treated with the ODN (s.c., 10 mg/mouse) at various schedules starting 12 h after the infection. The antibacterial efficacies of the ODN were evaluated by reducing bacterial growth in blood and organs as compared to those of control mice. In the results, bacteria grew in the blood (>105 CFU/ml), liver (>106 CFU/gram), spleen (>105 CFU/gram), and kidneys (>107 CFU/gram) of control mice 3 to 5 days after MRSA infection. However, significant growth of the pathogen in their organs was not demonstrated in SAB-mice treated with the ODN 12, 24, and 36 h after the infection. Similar results were obtained in SAB-mice orally infected with E. faecalis. These results indicate that infections with MRSA and E. faecalis in SAB-mice are controllable by the therapeutic treatment with CCL1 antisense ODN.