Grant: Travel Awards - Institute Community Support

Sepsis is the leading cause of morbidity and mortality in patients in the non-coronary ICU. However, the heterogeneity of patients with severe sepsis makes the identification of high-risk patients (ie. those who are sickest and thus would require more aggressive and expensive therapies) an ongoing challenge. We have shown that high levels of cell-free DNA (cfDNA) appear to be a powerful predictor of death in severe sepsis patients. The purpose of this study is to characterize the source and biochemical properties of cfDNA in sepsis. These studies are the first to characterize the source and biochemical properties of cfDNA in sepsis. A portion of cfDNA release from monocytes and neutrophils appears to occur via an apoptosis-independent mechanism, suggesting active release. Plasma levels of DNAse enzyme were reduced in septic patients compared to healthy volunteers. Arguably most importantly, however, we have shown that histones appear to increase the amount of tissue factor on both monocytes and HUVEC, suggesting that they are able to illicit a proinflammatory state that would contribute to the systemic coagulation and inflammation characteristic of sepsis.