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      Serum Cytokine Receptor Levels in Noninfectious Uveitis

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          Abstract

          Purpose: Understanding of the role of cytokines in uveitis may provide new clues to its treatment. Therefore, the purpose of our study was to evaluate systemic cytokine receptor expression in patients with noninfectious uveitis. Method: Serum concentrations of soluble interleukin-2 receptor α (IL-2 s Rα) and soluble tumor necrosis factor receptor-1 (sTNF-R1) were measured in patients with intermediate uveitis (n = 26), posterior uveitis (n = 23) and healthy controls (n = 12) using ELISA. All patients were identified in a consecutive series of 996 uveitis patients who had been diagnosed between 1998 and 2002 and classified according to the recommendations of the International Uveitis Study Group. Inclusion criteria were idiopathic, active intraocular inflammation, uveitis as a primary process and no systemic anti-inflammatory treatment at the time of blood sampling. None of the patients had an underlying systemic disease. Results: Serum concentrations of IL-2 s Rα were significantly increased in patients with posterior (p < 0.005) and intermediate uveitis (p < 0.005) as compared to healthy controls. Similarly, concentrations of sTNF-R1 appeared to be increased in posterior (p < 0.005) and intermediate (p < 0.005) uveitis patients when compared to controls. Conclusions: Our results may suggest that patients with noninfectious uveitis express systemic cytokine receptors such as TNF-R1 and IL-2 Rα, which may have an important role in the immune response of the eye and may lead to new immunomodulatory approaches.

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          Most cited references 18

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          Tumor necrosis factor: a pleiotropic cytokine and therapeutic target.

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          Advances in the molecular biology of human diseases indicate that the most striking manifestations of illness may be caused not by exogenous pathogenic or tumor products, but rather by toxic peptides produced by the host itself. Tumor necrosis factor (TNF), a polypeptide cytokine produced during infection, injury, or invasion, has proved pivotal in triggering the lethal effects of septic shock syndrome, cachexia, and other systemic manifestations of disease. Because removing TNF from the diseased host may prevent development of the illness, this factor has recently been the focus of intensive research. This review discusses the biology of this cytokine, with particular emphasis on its potential therapeutic role in septic shock and cachexia.
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            Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha.

            There are few effective treatments for ankylosing spondylitis, which causes substantial morbidity. Because of the central role of tumor necrosis factor alpha in the spondyloarthritides, we performed a randomized, double-blind, placebo-controlled trial of etanercept, a recombinant human tumor necrosis factor receptor (p75):Fc fusion protein, in patients with ankylosing spondylitis. Forty patients with active, inflammatory ankylosing spondylitis were randomly assigned to receive twice-weekly subcutaneous injections of etanercept (25 mg) or placebo for four months. The primary end point was a composite of improvements in measures of morning stiffness, spinal pain, functioning, the patient's global assessment of disease activity, and joint swelling. Patients were allowed to continue taking nonsteroidal antiinflammatory drugs, oral corticosteriods (< or =10 mg per day), and disease-modifying antirheumatic drugs at stable doses during the trial. Treatment with etanercept resulted in significant and sustained improvement. At four months, 80 percent of the patients in the etanercept group had a treatment response, as compared with 30 percent of those in the placebo group (P=0.004). Improvements over base-line values for various measures of disease activity, including morning stiffness, spinal pain, functioning, quality of life, enthesitis, chest expansion, erythrocyte sedimentation rate, and C-reactive protein, were significantly greater in the etanercept group. Longitudinal analysis showed that the treatment response was rapid and did not diminish over time. Etanercept was well tolerated, with no significant differences in rates of adverse events between the two groups. Treatment with etanercept for four months resulted in rapid, significant, and sustained improvement in patients with ankylosing spondylitis.
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              The natural history of uveitis.

               R Nussenblatt (1990)
              Inflammatory diseases of the eye were known to the ancients, but only recently have the underlying mechanisms to this problem become better defined. During the middle portion of this century, most cases of uveitis thought to be caused by infectious agents, such as those responsible for syphilis and tuberculosis. Since then, it has become clear that endogenous mechanisms of immunomodulation play an important role in these disorders, which along with environmental and genetic factors make up an important triad. Animals studies have indicated the pivotal role of the T-cell in many of these disorders. The development of T-cell lines has helped to further delineate cell to cell interactions that occur during an ocular inflammatory event. The presence in the eye of uveitogenic antigens raises the strong possibility of autoimmune driven processes as well, similar to what is seen in the animal models. The better understanding of ocular inflammatory mechanisms has led to improved therapeutic strategies, including Sandimmune, and more recently Cyclosporine G, a related compound that may be less nephrotoxic. Newer therapeutic strategies will focus on even more novel modes of immunomodulation, probably without the use of medications.
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                Author and article information

                Journal
                ORE
                Ophthalmic Res
                10.1159/issn.0030-3747
                Ophthalmic Research
                S. Karger AG
                0030-3747
                1423-0259
                2005
                April 2005
                20 May 2005
                : 37
                : 2
                : 112-116
                Affiliations
                aCharité, University School of Medicine Berlin, Campus Virchow Klinikum, Clinic of Ophthalmology, Berlin, Germany; bUniversidad Autónoma de Barcelona, Barcelona, Spain
                Article
                84271 Ophthalmic Res 2005;37:112–116
                10.1159/000084271
                15746567
                © 2005 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: 1, References: 29, Pages: 5
                Categories
                Original Paper

                Vision sciences, Ophthalmology & Optometry, Pathology

                Interleukin-2, Uveitis, TNF-α

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