Characterization of sepsis pathogenesis using molecular biomarkers and drug treatments in the mouse CLP model (56.6)

• Published in: The Journal of immunology (1950) Vol. 186; no. 1_Supplement; pp. 56 - 56.6
• Main Authors: Bender, Andrew, Wu, Yin, Burgess, Laurette, Teceno, Tyler, Skokanova, Eva, Cao, Qiongfang, Wilcoxen, Keith, Ishizaka, Sally, Shirota, Hiroshi
• Format: Journal Article
• Language: English
• Published: 01.04.2011
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.186.Supp.56.6

Abstract Sepsis is a severe systemic disease caused by an uncontrolled immune response to an inflammatory stimulus. Sepsis has a high mortality rate and few successful treatments are available. Furthermore, one of the confounding aspects of sepsis treatment is the highly variable and dynamic manifestation of the disease. Thus, there is a need not only for new sepsis treatments but also for biomarkers of sepsis that may guide physicians in patient treatment. The cecal ligation and puncture model (CLP) is a clinically relevant model that replicates the nature of human sepsis after trauma as it has a focus of infection rather than a systemic initiation. Thus, we have chosen to characterize the CLP model and use it to evaluate candidate sepsis biomarkers and therapeutics. We evaluated a variety of potential biomarkers and correlated them with body temperature to determine which ones best reflect the health of the animal. Interestingly, some cytokines and blood chemistry markers highly correlated with health and bacterial load while others did not. To gain further insight into sepsis pathogenesis we tested drugs with differing mechanisms of action. A significant observation was that an antibiotic was highly efficacious while the immunosuppressive dexamethasone was not beneficial; suggesting that bacterial elimination is crucial for survival. In summary, our results suggest potential biomarkers for guiding sepsis treatment and provide insight into sepsis pathogenesis.