Novel approaches for the supportive extracorporeal therapy of sepsis: Towards personalized treatment

Abstract

Sepsis and sepsis-associated multiple organ failure are associated with extensive tissue damage caused by over-activation of the innate immune system and by the excessive release of inflammatory mediators. The development of targeted therapies for sepsis remains a major challenge due to the complex network of inflammatory mediators involved in the septic process.

Early detection and timely therapeutic intervention are crucial for improved outcome of patients with sepsis. Currently however, the diagnosis of sepsis mostly relies on general symptoms. Taking into account the extreme heterogeneity of septic patients, the application of supportive extracorporeal therapies to modulate the concentration of inflammatory mediators requires diagnostic tools to monitor the inflammatory profile of the patients in order to identify the optimal time window for application of supportive therapies.

Here, we report on the development of extracorporeal adsorption systems for cytokine modulation and on the development and validation of a novel array technology to detect markers of inflammation (interleukins 6 and 10, C-reactive protein, procalcitonin, serum amyloid A) in a bedside-approach (detection from whole blood samples within 30 min). We demonstrate that the modulation of inflammatory mediators in septic plasma by means of selective adsorption significantly reduces endothelial activation in a cell culture model. We also discuss the role of extracellular microvesicles as markers and as potential targets for therapy.