Characterizing the kinetics of presepsin and associated inflammatory biomarkers in human endotoxemia

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 patients [1]. 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 the current state of infection.

The current 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 favorable 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 performance [2], 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 severity [2, 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 is currently hampered by poor characterization of their kinetics. Characterizing biomarker kinetics in severely ill 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. In this model, a systemic toll-like receptor 4 (TLR4)-mediated inflammatory response is induced by administering lipopolysaccharide (LPS). Although LPS challenge studies are considered a poor model of clinical sepsis, these studies may help to characterize specific components of the inflammatory responses, which play an important role in sepsis. 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.

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