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      Techniques of Extracorporeal Cytokine Removal: A Systematic Review of the Literature

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          Abstract

          Background and Aims: Attempts at achieving cytokine homeostasis include blood purification to deliver cytokine removal. Assessment of ex vivo studies for optimal operating conditions is a vital step. Methods: We conducted a systematic search for ex vivo studies on cytokine removal using known modalities of extracorporeal circulation. We selected 29 articles and analyzed data according to clearance, sieving coefficient, ultrafiltrate concentration and percentage removal. Results: We identified four main techniques for cytokine removal: standard techniques, high cut-off (HCO) techniques, adsorption techniques and combined plasma filtration adsorption. HCO hemofiltration (HCO/HF) showed greatest consistency in cytokine removal among all approaches. Mean albumin clearance with HCO filters was 3.74 ml/min. Conclusion: Ex vivo data support the view that HCO/HF is the most consistently effective approach in terms of sieving and clearance. Further investigation of HCO/HF in randomized controlled trials in animal models and humans seems desirable.

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          Most cited references 26

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          Inside, outside, upside down: damage-associated molecular-pattern molecules (DAMPs) and redox.

          Immune responses are initiated and perpetuated by molecules derived from microorganisms pathogen-associated molecular-pattern molecules or from the damage or death of host cells [damage-associated molecular-pattern (DAMP) molecules]. Many DAMPs are nuclear or cytosolic proteins with defined intracellular function that, when released outside the cell following tissue injury, move from a reducing to an oxidizing milieu resulting in their functional denaturation. Here, we discuss the consequences of DAMP oxidation on the outcome of acute inflammation. We also suggest that, outside the cell, DAMPs might adopt novel conformations or alter the redox of the extracellular environment to more closely mimic the internal one, thereby avoiding oxidation-mediated inactivation and promoting pathology. We propose that chronic inflammation associated with autoimmunity, chronic viral infection and cancer is probably mediated by persistent release and function of DAMPs, promoting and promoted by a disordered redox environment.
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            Sepsis: definition, epidemiology, and diagnosis.

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              Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-kappaB DNA binding, and improves short-term survival in lethal endotoxemia.

              Previous studies have shown that inflammatory mediators can be removed from the circulation with hemofiltration and that adsorption plays an important role. Because adsorptive capacity of hollow-fiber dialyzers is limited, we sought to determine whether hemoadsorption using high surface area beads would result in greater mediator removal and improved survival in experimental sepsis. Randomized controlled laboratory experiment. University laboratory. Sixty-six adult Sprague-Dawley rats. We conducted two ex vivo and two in vivo experiments. For in vivo experiments, we administered Escherichia coli endotoxin (20 mg/kg) by intravenous infusion and then randomized each animal to receive either hemoadsorption or a sham circuit for 4 hrs. Hemoadsorption was performed for 4 hrs using an arterial-venous circuit and a CytoSorb cartridge containing 10 g of polystyrene divinyl benzene copolymer beads with a biocompatible polyvinylpyrrolidone coating. Survival time was measured to a maximum of 12 hrs. In a separate set of experiments, we studied 12 animals using the same protocol except that we killed all animals at 4 hrs and removed standardized sections of liver for analysis of nuclear factor-kappaB DNA binding. Mean survival time among hemoadsorption-treated animals was 629+/-114 vs. 518+/-120 mins for sham-treated animals (p <.01). Overall survival (defined at 12 hrs) was also significantly better in the hemoadsorption group, seven of 20 vs. one of 20 (p <.05). Plasma interleukin-6 and interleukin-10 concentrations and liver nuclear factor-kappaB DNA binding were significantly reduced by hemoadsorption. Ex vivo experiments showed no endotoxin adsorption but strengthened our in vivo observations by showing rapid adsorption of tumor necrosis factor, interleukin-6, and interleukin-10. Hemoadsorption was associated with reduced inflammation and improved survival in this murine model of septic shock.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2012
                March 2012
                13 January 2012
                : 33
                : 1-3
                : 88-100
                Affiliations
                aDepartment of Intensive Care, Austin Hospital, Heidelberg, Vic., Australia; bJohor Bahru Clinical School, Monash University Sunway Campus, Johor Bahru, Malaysia
                Author notes
                *Prof. Rinaldo Bellomo, Department of Intensive Care, Austin Hospital, Studley Road, Heidelberg, Melbourne, VIC 3084 (Australia), Tel. +61 3 9496 5992, E-Mail rinaldo.bellomo@austin.org.au
                Article
                333845 Blood Purif 2012;33:88–100
                10.1159/000333845
                22248671
                © 2012 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 2, Tables: 6, Pages: 13
                Categories
                Original Paper

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