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      A Switch to High-Flux Helixone ® Membranes Reverses Suppressed Interferon-γ Production in Patients on Low-Flux Dialysis

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          Abstract

          Long-term hemodialysis (HD) induces an inflammatory response and is associated with a suppressed cellular immune response manifested, in part, by impaired interferon (IFN-γ) production. We investigated the effect of high-flux HD using the synthetic Helixone<sup>®</sup> membrane and ultrafiltered dialysate on plasma levels of inflammatory mediators and on the whole blood production of IFN-γ. Methods: Twelve ESRD patients were dialyzed under low-flux HD (polysulfone F6) and again after 6 weeks of high-flux HD (Helixone<sup>®</sup> FX100). Ultrafiltered bicarbonate dialysate without bacterial growth and no detectable endotoxin was used throughout the study. Plasma levels of urea, albumin, β<sub>2</sub>-microglobulin (β<sub>2</sub>-m), interleukin (IL)-6, C-reactive protein (CRP), IL-1 receptor antagonist (IL-1Ra), IL-18, and IL-18-binding protein (IL-18BP) were measured. In addition, the Staphylococcus epidermidis-induced production of IFN-γ and IL-18 was assessed in whole blood cultures of HD patients as well as in 9 healthy subjects. Results: Plasma levels of urea, albumin, IL-6, IL-1Ra and CRP were not significantly different between high-flux and low-flux HD. In contrast, β<sub>2</sub>-m levels decreased significantly by 31% with high-flux Helixone<sup>®</sup> (p < 0.002). Stimulated whole blood production of IFN-γ was reduced in low-flux HD but increased to near normal levels after 6 weeks of high-flux HD. Plasma levels of free IL-18 and its specific inhibitor IL-18BP were not different between the two dialyzer membranes. Conclusion: Compared to low-flux polysulfone HD with ultrafiltered dialysate, high-flux HD with the synthetic Helixone<sup>®</sup> membrane did not result in a significant change in plasma levels of proinflammatory (IL-6, CRP, IL-18) and anti-inflammatory (IL-1Ra, IL-18BP) cytokines. However, high-flux HD restores whole blood IFN-γ production without significant changes in free IL-18. Therefore, the immune modulation in high-flux HD is likely due to removal of inhibitors of IFN-γ production other than IL-18BP.

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          Most cited references 4

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          Interleukin-18 Binding Protein

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            Structural requirements of six naturally occurring isoforms of the IL-18 binding protein to inhibit IL-18

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              Chronic Inflammation in Hemodialysis: The Role of Contaminated Dialysate

              Routine sodium bicarbonate-buffered dialysate is contaminated with predominantly gram-negative micro-organisms. These bacteria release pyrogenic substances such as endotoxins, peptidoglycans, exotoxins and fragments thereof. Pyrogens derived from contaminated dialysate either alone or in costimulation with activated complement components are the most important activators of circulating mononuclear cells in patients on chronic intermittent hemodialysis. Activated mononuclear cells release proinflammatory cytokines which are key mediators in acute and chronic inflammatory diseases associated with long-term hemodialysis therapy. Recent experimental and clinical data suggest that the use of pyrogen-free dialysate prevents activation of mononuclear cells and improves the state of chronic inflammation, as indicated by decreased plasma levels of C-reactive protein in chronic hemodialysis patients. Future clinical studies have to prove whether the use of pyrogen-free dialysate in combination with biocompatible dialyzer membranes and tubings reduces the incidence and severity of chronic inflammatory diseases (β 2 -microglobulin amyloidosis, muscle protein wasting, atherosclerosis) in long-term hemodialysis patients.
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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
                2003
                2003
                05 June 2003
                : 21
                : 3
                : 225-231
                Affiliations
                aGemeinschaftspraxis Nephrologie/Dialyse, Langenhagen and bFresenius Medical Care, Bad Homburg, Germany; cDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel; dDepartment of Medicine, University of Colorado Health Science Center, Denver, Colo., USA
                Article
                70694 Blood Purif 2003;21:225–231
                10.1159/000070694
                12784048
                © 2003 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: 4, Tables: 2, References: 16, Pages: 7
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/70694
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