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.
Highlights
Sepsis has been defined as life-threatening organ dysfunction caused by a dysregulated host response to infection [1]
This study demonstrates that CytoSorb® hemoadsorbent polymer beads efficiently remove a broad spectrum of toxic pathogen-associated molecular pattern molecules (PAMPS) and DAMPS from blood providing an additional means of reducing the uncontrolled inflammatory cascade that contributes to a maladaptive systemic inflammatory response syndrome (SIRS) response, organ dysfunction and death in patients with a broad range of life-threatening
As stated in the author contributions, CytoSorbents Corporation had a role in the study design, decision to publish and editing of the manuscript
Summary
Sepsis has been defined as life-threatening organ dysfunction caused by a dysregulated host response to infection [1]. Numerous factors contribute to this dysregulation, including proinflammatory and anti-inflammatory cytokines, pathogen-associated molecular patterns (PAMPs) such as bacterial exotoxins and endotoxins, mycotoxins, damage-associated molecular patterns (DAMPs) released by injured cells, and host-specific factors such as activated complement and procalcitonin. Complex interactions involving such substances can lead to severe immune system dysfunction ranging from a destructive maladaptive systemic inflammatory response syndrome (SIRS) to advanced immunosuppression. Once released into the bloodstream [2], DAMPs, like PAMPs, trigger immune responses through pattern recognition receptors [3]. Persistent circulating DAMP elevations contribute to organ injury [4] and identify those patients at highest risk of multiple organ dysfunction syndrome and death in community-acquired pneumonia and sepsis [5]
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