Effect of CCL1 antisense oligodeoxynucleotides (ODN) on MRSA infection in subacutely burned mice (SB-mice) (MPF3P.810)

Abstract

Abstract Staphylococcus aureus is frequently isolated from subacutely burned patients, and these infections easily develop into severe sepsis. M2bMφ have been characterized as the responsible cells on the increased susceptibility of SB-mice to staphylococcal infections, and SB-mice are carriers of M2bMφ. In this study, we tried to protect SB-mice (mice 10 to 30 days after burn injury) from a lethal dose infection of MRSA using CCL1 antisense ODN (an inhibitor of M2bMφ). Mice, 14 days after burn injury (20% total body surface area 3rd degree burns), were infected with 2 x 106 CFU/mouse of MRSA. Then, these mice were treated s.c. with 10 μg/mouse of CCL1 antisense ODN twice a day for 3 days (treated mice). As control mice, SB-mice were treated with scrambled ODN. The protective effect of the ODN against MRSA infection was evaluated by a reduction in the mortality rates of treated mice as compared with that of control mice. Also, bacterial growth in various organs of treated mice was compared with those of controls. In the results, all control mice died within 7 days of MRSA infection, while all treated mice were still alive after 7 days with the same infection. Bacteria grew in the liver, spleen and kidneys of control mice. However, the pathogen did not grow significantly in these organs of treated mice. These results indicate that sepsis caused by a lethal dose of MRSA infection in SB-mice is controlled by treatment with CCL1 antisense ODN.