Assessment of the necroptotic pathway in septic patients and its correlation with disease severity and patient's clinical parameters

Abstract

Sepsis, an acute systemic inflammatory response, is a severe condition that leads to death in approximately 30% of the cases. It has enormous economic impact, generally accounting for more than a third of overall hospital costs. Despite the recent findings, the mechanisms involved in the initiation and progression of sepsis are not fully elucidated, which hampers our ability to fight this disease. One of the hallmarks of septicemia is the massive death of immune cells. Necroptosis, a recently discovered cell death mode, has a high inflammatory potential and it has been shown to be involved with pathologies associated with inflammation and infection. In animal models of sepsis, mice deficient in necroptotic components or treated with necroptosis inhibitors presented lower mortality rates as well as fewer and attenuated organ dysfunctions, indicating that necroptosis contributes to the deleterious effects of sepsis. To date, however, there is no data regarding the association of necroptosis and sepsis in human patients. Therefore, this project will investigate whether there is an increase in the necroptosis levels in peripheral blood cells from patients with sepsis compared to control patients and whether it is possible to establish a correlation between necroptosis levels and the severity of the disease. Altogether, the data generated in this study may unveil novel prognostic markers for the presence and severity of sepsis. Further, it might as well as indicate new and exciting targets for therapeutic intervention. (AU)