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      Usefulness of a Highly Sensitive Urinary and Serum IL-6 Assay in Patients with Diabetic Nephropathy

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          Abstract

          Background/Aim: Interleukin-6 (IL-6) promotes the growth of renal mesangial cells. IL-6 may play a major role in such mesangial proliferation, but there has been little research on IL-6 in relation to diabetic nephropathy because of the difficulty in measuring urinary and serum IL-6 levels. Using a newly developed, highly sensitive IL-6 assay, we studied the relationship between serum and urinary IL-6 and diabetic nephropathy. Methods: We investigated 72 patients with type 2 diabetes. Urinary and serum IL-6 concentrations were measured using a chemiluminescent enzyme immunoassay with a detection limit of 0.11 pg/ml. Results: There was a significant increase of the serum IL-6 level as diabetic nephropathy progressed, with the level being 1.4 ± 0.3 pg/ml in patients with normal albuminuria, rising to 2.4 ± 0.6 pg/ml in patients with microalbuminuria and then to 4.4 ± 0.8 pg/ml in those having proteinuria. The serum IL-6 level was also significantly correlated with fibrinogen and aortic pulse wave velocity. The urinary IL-6 level was also significantly increased in diabetic patients as nephropathy progressed. Both serum and urinary IL-6 levels were high in the group with nephropathy, but there was no correlation between the two. Conclusion: The urinary IL-6 level seems to be a good indicator of diabetic nephropathy, and atherosclerotic changes were related to the serum IL-6 level. The serum IL-6 may, therefore, be useful in the evaluation of atherosclerosis including nephropathy.

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          Interleukin-6 and interleukin-8 protein and gene expression in human arterial atherosclerotic wall.

          Interleukin 6 (IL-6) and interleukin 8 (IL-8) are present in the human arterial atherosclerotic wall as cellular and extracellular deposits in the connective tissue matrix. Quantitative determinations of IL-6 by ELISA showed mean values of 27.6 +/- 3.3 ng/100 mg protein in normal intima, 37.3 +/- 2.1 ng/100 mg protein in fibrous plaque and 25.7 +/- 4.3 ng/100 mg total extracted protein in media. IL-8 levels were 3.5 +/- 0.6 ng/100 mg protein in normal intima, 11.3 +/- 2.1 ng/100 mg protein in fibrous plaque and 8.5 +/- 1.4 ng/100 mg total extracted protein in media. Fibrous plaques presented statistically significant higher levels of both IL-6 and IL-8. IL-6 and IL-8 gene transcripts were present in human iliac fibrous plaque and media prelevated at surgery indicating that a local production by the cells of the arterial wall participate to their accumulation. We also tested the role of complement activation in induction of IL-6 and IL-8 protein synthesis as well as the subsequent activation of endothelial cells. Only IL-8 was induced by complement activation and this may contribute to increased IL-8 levels found in the atherosclerotic wall. When exposed to terminal complement complexes, endothelial cells in culture also showed an increase of both DNA-synthesis and p70 S6 kinase activity indicating that complement is able to induce not only IL-8 synthesis but also cell activation. The presence of IL-6 and IL-8 in the arterial wall where complement activation also occurred, clearly show the involvement of inflammatory events in initiation and progression of atherosclerosis.
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            Author and article information

            Journal
            NEF
            Nephron
            10.1159/issn.1660-8151
            Nephron
            S. Karger AG
            1660-8151
            2235-3186
            2000
            May 2000
            21 April 2000
            : 85
            : 1
            : 81-85
            Affiliations
            aDepartment of Nephrology, Fujita Health University, Toyoake, and bDepartment of Internal Medicine, Ogaki Municipal Hospital, Ogaki, Japan
            Article
            45634 Nephron 2000;85:81–85
            10.1159/000045634
            10773760
            © 2000 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: 3, Tables: 1, References: 24, Pages: 5
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/45634
            Categories
            Preliminary Communication

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