Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins, and cytokines from whole blood using CytoSorb® sorbent porous polymer beads

Abstract

ObjectiveSepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis and septic shock, pathogen-associated molecular pattern molecules (PAMPS), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host often leading to excessive cytokine production, a maladaptive systemic inflammatory response syndrome response (SIRS), and tissue damage that releases DAMPs, such as activated complement and HMGB-1, into the bloodstream causing further organ injury. Cytokine reduction using extracorporeal blood filtration has been correlated with improvement in survival and clinical outcomes in experimental studies and clinical reports, but the ability of this technology to reduce a broader range of inflammatory mediators has not been well-described. This study quantifies the size-selective adsorption of a wide range of sepsis-related inflammatory bacterial and fungal PAMPs, DAMPs and cytokines, in a single compartment, in vitro whole blood recirculation system.Measurements and main resultsPurified proteins were added to whole blood at clinically relevant concentrations and recirculated through a device filled with CytoSorb® hemoadsorbent polymer beads (CytoSorbents Corporation, USA) or control (no bead) device in vitro. Except for the TNF-α trimer, hemoadsorption through porous polymer bead devices reduced the levels of a broad spectrum of cytokines, DAMPS, PAMPS and mycotoxins by more than 50 percent.ConclusionsThis study demonstrates that CytoSorb® hemoadsorbent polymer beads efficiently remove a broad spectrum of toxic PAMPS and DAMPS from blood providing an additional means of reducing the uncontrolled inflammatory cascade that contributes to a maladaptive SIRS response, organ dysfunction and death in patients with a broad range of life-threatening inflammatory conditions such as sepsis, toxic shock syndrome, necrotizing fasciitis, and other severe inflammatory conditions.

Retracted Article: High performance liquid chromatography coupled with high resolution mass spectrometry-based characterization of lipidomic responses from rats with kidney injuries

“…The source of the infection can lead to an uncontrollable inammatory cascade; due to continuity differences, its effects are different to human pathogenesis. [16][17][18] In addition, due to different operating intensities it is difficult to standardize for comparison among diverse groups, and so this experiment did not use the CLP model. Although the bacterial infusion or instillation model is easy to operate, the model is greatly affected by bacterial species, inoculum size, susceptible sites and infection routes leading to poor stability.…”

Extracorporeal Blood Purification Therapies for Sepsis

“…The CytoSorb ® technology (CytoSorbents, Monmouth Junction, NJ, USA) is an hemoperfusion cartridge filled with polymer beads that can adsorb pro-and antiinflammatory mediators, but not endotoxins [41]. In vitro experiments have shown removal rates of cytokines > 90-95% [42].…”

Clinical Utility of Extracorporeal Cytokine Hemoadsorption Therapy: A Literature Review

“…Particles outside this size range, including larger immune cells and smaller serum electrolytes recirculate unchanged. While the manufacturer states that bacterial endotoxins are not removed with CytoSorb, a study has shown some efficacy in removing toxins within the 5-60 kDa range [92].…”