Effect of IL-10 antisense gene therapy in severely burned mice intradermally infected with MRSA.
The effect of IL-10 antisense oligodeoxynucleotides (ODN) on the susceptibility of burned mice to intradermal (i.d.) infection of methicillin-resistant Staphylococcus aureus (MRSA) was studied. Abscesses formed and sepsis did not develop in normal mice infected i.d. with 10(8)CFU/mouse of MRSA. Similarly, sepsis caused by MRSA i.d. infection did not develop and abscesses formed in burned mice treated with IL-10 antisense ODN. However, all of the burned mice treated with scrambled ODN (control group) died by infectious complications stemming from MRSA i.d. infection, and an MRSA-abscess did not form in these mice. Macrophages (Mϕ) isolated from the infection site tissue of burned mice that were treated with IL-10 antisense ODN were identified as M1Mϕ, while Mϕ isolated from burned mice that were treated with scrambled ODN were shown to be M2Mϕ. MRSA-abscesses formed in burned mice inoculated with M1Mϕ, and these mice resisted a lethal dose of MRSA i.d. infection. However, an abscess did not form, and sepsis caused by MRSA i.d. infection developed in burned mice that were inoculated with M2Mϕ. These results indicate that severely burned mice treated with IL-10 antisense ODN are resistant against i.d. infection with MRSA. M1Mϕ appeared in the infection site tissues of severely burned mice that were treated with IL-10 antisense ODN may play a role on the abscess formation and inhibiting sepsis caused by MRSA i.d. infection.
Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555-0435, USA.
Akira
A
Asai
Mari
M
Kogiso
Makiko
M
Kobayashi
David N
DN
Herndon
Fujio
F
Suzuki
D000038:Abscess / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D002056:Burns / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D007271:Injections, Intradermal; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D012720:Severity of Illness Index; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology
D000900:Anti-Bacterial Agents; D016376:Oligonucleotides, Antisense; D016753:Interleukin-10