Genetic background determines susceptibility during murine septic peritonitis

Background. The tolerance of mouse strains to cecal ligation and puncture (CLP), a clinically relevant model of sepsis, can vary greatly. We compared the immune response and bacterial eradication during CLP in two mouse strains with different susceptibilities to the lethal effects in an effort to understand alterations in tolerance. Materials and methods. CLP of increasing severity was performed on Swiss Webster mice. Interleukin (IL)-12 levels, bacterial counts, and myeloperoxidase were determined. We then compared the same parameters in Swiss Webster and in BALB/c mice and determined survival for both mouse strains after CLP. Results. Bacterial counts locally and systemically as well as serum IL-12 correlated with the severity of CLP in Swiss Webster mice. Lung myeloperoxidase increased with increasing severity CLP, while peritoneal myeloperoxidase decreased. Following CLP, one-half of the Swiss Webster mice survived versus none of the BALB/c mice. Despite worsened survival, BALB/c mice had lower bacterial counts and similar IL-12 levels compared to Swiss Webster mice. Myeloperoxidase and IL-6 levels were similar between experimental groups. Conclusions. Swiss Webster and BALB/c mice have significantly different susceptibilities to the lethal effects of CLP, and this difference may be related to IL-12 responsiveness. (C) 2002 Elsevier Science.