Assessment of necroptosis in patients with sepsis and septic shock

Abstract

Sepsis, an acute systemic inflammatory response, is a severe condition that leads to death in approximately 30% of the cases. Despite the recent findings, the mechanisms involved in the initiation and progression of sepsis are not fully elucidated, which hampers our ability to treat this condition. One of the hallmarks of sepsis 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. We hypothesize that necroptosis could contribute to inflammation, cell destruction and organ dysfunction in patients with sepsis. Therefore, this collaborative 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. (AU)