Clinical Validation of a Murine Model of Sepsis: Defining Thresholds for Deterioration

METHODS: We used CCR2 Depleter (DTR) mice that express a functional diphtheria toxin receptor under the control of CCR2 promoter. In these mice, CCR2-expressing monocytes and macrophages are selectively eliminated with diphtheria toxin treatment. Although the control mice receive the same treatment, their CCR2 positive cells remain intact. The immunologic status of these septic animals was assessed by measuring cytokine levels and bacterial counts from blood, peritoneal lavage fluid, and vital organs 6 and 16 hours after CLP in CCR2 DTR and control (CO) mice. Survival and various markers of tissue damage were assessed as well.