Severe bacterial infections and sepsis are characterized by a systemic immune response. Inflammation-associated proteins can hold potential as treatment efficacy biomarkers. Such biomarkers can be utilized to monitor antibiotic therapy and inform treatment optimization, aiming to improve outcomes in patients1. It is essential that treatment efficacy biomarkers have a short induction time, a relatively rapid half-life, and closely follow the course of infection to reflect treatment response and/or disease progression.
The currently used biomarkers of infection, such as leukocyte counts and C-reactive protein (CRP), are either non-specific or suffer from a delayed onset of production and slow half-life. Identifying novel biomarkers with more favourable properties could improve the utility of biomarker guided treatments in severe infections and sepsis. Additionally, using a combination of different biomarkers has been shown to improve predictive performance2, suggesting the importance of understanding correlation in biomarker kinetics. Presepsin is emerging as a potential biomarker to inform treatment of infections and sepsis, and is associate with clinical disease severity2,3. However, the kinetics of presepsin, and how it relates to other established biomarkers, is poorly understood.
The clinical utility of treatment response biomarkers for infection and sepsis are currently hampered by poor characterization of their kinetics. Characterizing biomarker kinetics in severely ill and septic patient is challenging due to the heterogeneity in underlying infection or disease state. Experimental endotoxemia in healthy volunteers resembles some features of the inflammatory response during infection and sepsis, and may help to better understand specific components of the inflammatory responses that play a critical role in sepsis. In this model, a systemic toll-like receptor 4 (TLR-4) mediated inflammatory response is induced by administering lipopolysaccharide (LPS).
In the current study, we evaluated presepsin response in a human LPS challenge model, related the response to more standard inflammatory biomarkers, and characterized the kinetics of the response.