Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Observational
Official Title: Effect of Resistin on Neutrophil Function in Patients With Septic Shock and Acute Kidney Injury
Brief Summary:
Sepsis-induced immunosuppression affects all types of immune cells. Neutrophils are pivotal components of innate immunity and provide the first line of defense against invading microorganisms. After recruitment to the site of invading microorganisms, they phagocytose, kill and digest the microorganisms via well-orchestrated processes involving reactive oxygen species (ROS). However, neutrophils in sepsis demonstrate an immunosuppressed phenotype.(1) Reduced bacterial clearance, diminished production of reactive oxygen species (ROS), and impaired recruitment to the site of infection are the most prominent features.(2-4) Available data also reveal that neutrophil dysfunction develops prior to secondary infections, and patients with the most severely impaired neutrophil function carry the highest risk for secondary infections.(3) However, the mechanisms involved are still poorly understood.
Hyperresistinemia in sepsis has been associated with a greater disease severity and a worse outcome.(5-7). The Investigator's prior work in vitro has demonstrated that hyperresistinemia reversibly hinders neutrophil migration by impairing F-actin formation.(8) The current project revolves around the overall hypothesis that resistin also impairs bacterial killing by inhibiting the intracellular generation of reactive oxygen species.
While the study team has accumulated preliminary in vitro data supporting the inhibitory effect of resistin on neutrophils, it is imperative to confirm these findings in vivo. Specifically, the study team will need to study how serum resistin levels differ in patients with septic shock and acute kidney injury (AKI). Furthermore, it is essential to see how neutrophil function differs when exposed to serum from these two different patient populations (septic shock versus septic shock + AKI).