Comparison of the mortality and inflammatory response of two models of sepsis: Lipopolysaccharide vs. cecal ligation find puncture

Sepsis remains a serious clinical problem despite intense efforts to improv e survival. Experimental animal models of sepsis have responded dramaticall y to immunotherapy blocking the activity of cytokines. Despite these precli nical successes, human clinical trials have not demonstrated any improvemen t in survival. We directly compared the mortality, morbidity, and immunopat hology in two models of sepsis, one due to lipopolysaccharide (LPS) and the other to cecal ligation and puncture (CLP). BALB/c mice were injected intr aperitoneally with 250 mu g of LPS or subjected to CLP with an 18-gauge nee dle. Both models yielded similar mortality (> 85%) and morbidity. Additiona lly, neutropenia and lymphopenia developed in both groups. Plasma and perit oneal levels of cytokines (TNF, IL-l, IL-6, and the chemokines KC and MIP-2 ) were measured at 1.5, 4, and 8 h after challenge. LPS induced substantial ly higher levels of cytokines in both compartments with peak levels between 1.5 and 4 h that began to decline at 8 h. In contrast, cytokine levels in the CLP model were continuing to increase at the 8 h-time point and often e xceeded the LPS-induced values at this time. Our data demonstrate that the LPS and CLP models have similar mortality but significant differences in th e kinetics and magnitude of cytokine production. Immunotherapy for sepsis b ased on cytokine production after LPS challenge is misdirected because the LPS model does not accurately reproduce the cytokine profile of sepsis.