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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Induction of Cytokines and Adhesion Molecules in Stable Hemodialysis Patients: Is There an Effect of Membrane Material?

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          Abstract

          Background/Aims: The aim of this study was to examine the effects of a biocompatible and a nonbiocompatible hemodialysis membrane on the secretion of cytokines and their specific antagonists as well as on the expression of adhesion molecules. Methods: A crossover study using cuprophane (CU) and polysulfone (PS) dialyzers and measurements of serum tumor necrosis factor (TNF)-alpha, soluble TNF receptors, interleukin (IL)-6, IL-6 receptor, IL-2 receptor, IL-1 receptor antagonist and the adhesion molecules intercellular adhesion molecule 1, endothelial leukocyte adhesion molecule and vascular cell adhesion molecule was performed in 19 hemodialysis patients. 44 healthy volunteers served as controls. Results: All of the measured cytokines and cytokine antagonists as well as all adhesion molecules were significantly elevated in hemodialysis patients compared to controls. There was a significant increase in TNF-alpha during a dialysis session with a CU dialyzer, but only a moderate increase using a PS dialyzer. None of the other cytokines and adhesion molecules were changed during a dialysis session. We were also able to show an upregulation of adhesion molecules in dialysis patients. Conclu sion: Our study clearly demonstrates that levels of inflammatory cytokines as well as their antagonists and adhesion molecules are elevated in patients on hemodialysis therapy. Baseline values before the start of a dialysis session did not show any differences with regard to the usage of CU or PS dialysis membranes. However, CU dialyzers led to a significantly greater stimulation of TNF-alpha during the dialysis session in comparison to PS membranes, suggesting a higher degree of bioincompatibility.

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          Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor.

          Three interleukin-1 inhibitors have been purified to homogeneity from medium conditioned by human monocytes. Partial sequence analysis and digestion with N-glycanase indicate that these are glycosylation forms of a single protein. The protein binds to the interleukin-1 receptor but has no interleukin-1-like activity, even at very high concentrations, and is therefore a pure receptor antagonist.
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            Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro.

            Clinical and experimental evidence suggests that shock, arthritis, osteoporosis, colitis, leukemia, diabetes, wasting and atherosclerosis are mediated, in part, by interleukin 1 (IL-1). Inhibition of this cytokine has been a strategy for studying disease and for new drug development. A naturally-occurring IL-1 inhibitor (IL-1 receptor antagonist, IL-1ra) that blocks binding of IL-1 to its receptors has been cloned and produced in recombinant organisms. IL-1ra reduces the severity of sepsis, colitis, arthritis and diabetes in animals and is presently being tested in humans with arthritis, shock and myelogenous leukemia.
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              Interleukin-1 receptor antagonist reduces mortality from endotoxin shock.

              About five out of 1,000 patients admitted to hospital develop bacterial sepsis leading to shock, the mortality rate for which is high despite antibiotic therapy. The infection results in hypotension and poor tissue perfusion, and eventually leads to the failure of several organ systems. Bacterial endotoxin is thought to be the direct cause of shock in Gram-negative sepsis, because it can cause shock in animals, and antibodies against endotoxin prevent Gram-negative shock in animals and in humans. But, the symptoms of septic shock are the result of the actions of host cytokines induced by the endotoxin. The cytokine interleukin-1 has been implicated as an important mediator of septic shock because it can induce tachycardia and hypotension and act synergistically with tumour necrosis factor to cause tissue damage and death. We now report that a specific interleukin-1 receptor antagonist reduces the lethality of endotoxin-induced shock in rabbits, indicating that interleukin-1 does indeed play an important part in endotoxin shock.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2003
                December 2003
                21 November 2003
                : 23
                : 6
                : 442-447
                Affiliations
                Klinik und Poliklinik für aInnere Medizin II und bInnere Medizin I, Universität Regensburg, cCaritas-Krankenhaus St. Josef, Regensburg, Deutschland
                Article
                74536 Am J Nephrol 2003;23:442–447
                10.1159/000074536
                14583663
                21edc5ee-c268-4ae6-8bff-e0dcdf249bc1
                © 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.

                History
                : 17 March 2003
                : 08 July 2003
                Page count
                Tables: 2, References: 38, Pages: 6
                Categories
                Original Report: Patient-Oriented, Translational Research

                Cardiovascular Medicine,Nephrology
                Cuprophane,Cytokines,Hemodialysis,Polysulfone,Adhesion,Biocompatibility
                Cardiovascular Medicine, Nephrology
                Cuprophane, Cytokines, Hemodialysis, Polysulfone, Adhesion, Biocompatibility

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