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. 2018 Jan 25;13(1):e0191676.
doi: 10.1371/journal.pone.0191676. eCollection 2018.

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

Maryann C Gruda  1 , Karl-Gustav Ruggeberg  1 , Pamela O'Sullivan  1 , Tamaz Guliashvili  1 , Andrew R Scheirer  1 , Thomas D Golobish  1 , Vincent J Capponi  1 , Phillip P Chan  1
Affiliations

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

Maryann C Gruda et al. PLoS One. .

Abstract

Objective: Sepsis 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 results: Purified 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.

Conclusions: This 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.

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Conflict of interest statement

Competing Interests: Authors Phillip P. Chan, MD, PhD and Vincent J. Capponi, MS, serve as the Chief Executive Officer and Chief Operating Officer of CytoSorbents Corporation, respectively. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Adsorption of cytokines from whole blood with CS hemoadsorptive polymer beads or a control (no polymer) device.
Percent remaining from the mean ± SEM of 4 runs. * p<0.05.
Fig 2
Fig 2. Adsorption of DAMPs from whole blood with CS hemoadsorptive polymer beads or a control (no polymer) device.
Percent remaining from the mean ± SEM of 4 runs per analyte. * p<0.05.
Fig 3
Fig 3. Adsorption of bacterial PAMPs with CS hemoadsorptive polymer beads or a control (no polymer) device from whole blood spiked with S. pyogenic exotoxin B, Staph TSST-1 or serum with Staph aureus alpha-toxin.
Percent remaining from the mean ± SEM of 4 runs. * p<0.05.
Fig 4
Fig 4. Adsorption of mycotoxins with CS hemoadsorptive polymer beads or a control (no polymer) device from whole blood spiked with A. flavus aflatoxin B1 (10 mg/L) or Fusarium T-2 toxin (10 mg/L).
Percent remaining from the mean ± SEM of 4 runs. * p<0.05.
See this image and copyright information in PMC

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