Immunopathologic responses to non-lethal sepsis

Although sepsis causes significant morbidity and mortality, its basic patho logy is still not well understood. We investigated the inflammatory and phy siologic alterations of non-lethal sepsis using cecal ligation and puncture (CLP), a model that induces peritonitis due to mixed intestinal flora, rep roducing the complex immunology of sepsis. Groups of mice were subjected to CLP (25G needle) or sham surgery, had minimitters implanted to continuousl y monitor temperature and activity, and were sacrificed daily for 6 days. T here was significant hypothermia (6-13 hrs post-surgery), and decreases in activity (to day 4) and weight (to day 3) but no mortality in the CLP group . Blood analyses of the CLP-treated mice showed reduced hemoglobin, platele ts, lymphocytes, monocytes, and neutrophils, compared to sham animals. Both groups had nearly equivalent neutrophil influx into the peritoneum. Plasma and peritoneal G-CSF, IL-6, as well as the murine chemokines KC and MIP2-a lpha were significantly higher in the CLP-treated mice at day 1. Plasma and peritoneal TNF were low (<70 pg/mL). While there was elevated IL-1 beta in the peritoneum of the CLP-treated mice, this cytokine was not detected in the plasma in either treatment group. Cytokines were not detected in the pu lmonary airspace of the CLP-treated mice and PMNs were not recruited to thi s site. Our data shows altered immunopathology in non-lethal sepsis with si gnificant blood and cytokine alterations. Since there was 100% survival, th e inflammatory response was appropriate and probably even protective.