Steroid Hormones and the T-Cell ~ Cytokine Profile

Steroid Hormones and the T-Cell ~ Cytokine Profile

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G.A.W. Rook and S. Lightman (Eds) Steroid Hormones and the T-Cell Cytokine Profile With 51 Figures Springer

Professor G.A.W. Rook Department of Bacteriology, UCL Medical School, Windeyer Building, 46 Cleveland Street, London WIP 6DB, UK Professor S. Lightman Department of Medicine, Dorothy Hodgkin Crowfoot Laboratories, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, UK ISBN-13: 978-1-4471-1238-9 British Library Cataloguing in Publication Data Steroid hormones and the T-cell cytokine profile l.immune response - Regulation 2.Steroid hormones - Therapeutic use I.Rook, Graham A. w. II.Lightman, Stafford 1. (Stafford Louis) 571.9'646 ISBN -13:978-1-4471-1238-9 3. T -cells Library of Congress Cataloging-in-Publication Data Steroid hormones and the T-cell cytokine profile 1 G.A.W Rook and S. Lightman, eds. p. cm. Includes bibliographical references and index. ISBN-13: 978-1-4471-1238-9 e-jsbn-13:978-1-4471-0931-0 DOI: 10.1007/978-1-4471-0931-0 1. Glucocorticoids - Immunology. 2. T cells. 3. Cytokines. 4. Immune response - Regulation. I. Rook, G. A. W. (Graham A. W.), 1946-. II. Lightman, Stafford 1. [DNLM: 1. Immunity, Cellular - drug effects. 2. Steroids - immunology. 3. Steroids - pharmacology. 4. Cytokines - drug effects. 5. T-Lymphocytes - drug effects. 6. Anti- Inflammatory Agents, Steroidal- pharmacology. QW 568 S838 1997] QP572.G54S74 1997 616.07'9 - DC2l DNLM/DLC for Library of Congress 97-15904 Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent to the publishers. Springer-Verlag London Limited 1997 Softcover reprint of the hardcover I st edition 1997 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore free for general use. Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Typeset by EXPO Holdings, Malaysia 28/3830-543210 Printed on acid-free paper

Preface The fact that certain adrenal steroid hormones are immunosuppressive and anti-inflammatory has been known for many years, and is routinely exploited by physicians. These effects are attributable to glucocorticoid steroids such as cortisol. Pharmacological doses of glucocorticoids inhibit most or all T cell types. However we now know that the effect of exposure to raised physiological levels is mainly to drive developing lymphocyte responses towards a Th2 cytokine profile (interleukin-4 secreting) while suppressing the development ofthi (gamma interferonsecreting) lymphocytes. Only recently have two further regulatory mechanisms become apparent. First, these effects of cortisol are balanced by pro-inflammatory and ThI-enhancing effects of another adrenal steroid, dehydroepiandrosterone sulfate (DHEAS). Second, the activity of cortisol is directly modulated by enzymes in the target organs and lymphoid tissues that convert it into inactive cortisone. This new information leads to the possibility that immunoregulatory steroids could be used by physicians in novel ways. We can envisage steroid combinations that exploit the anti-inflammatory effects of cortisol, while the Thi-suppressing and Th2-promoting properties of these hormones are opposed by derivatives of DHEAS. Such therapies are already proving effective in animal models of infection, and could revolutionize treatment of Th2-mediated diseases such as asthma, where the anti-inflammatory effects of cortisol are desirable but the effects on T lymphocyte differentiation are not. Alternatively, steroid analogues may be used to inhibit the enzymes that inactivate cortisol, or those that generate the DHEAS derivatives that oppose cortisol's functions, and in this way the effects of endogenous cortisol may be enhanced without administration of cortisol itself. This book provides an overview of these new concepts, starting with accounts of how the immune response triggers adrenal steroid production, and finishing with in vivo models of infection and autoimmunity that demonstrate the clinical importance of these new insights into the physiological control of glucocorticoid function. The information contained is mostly very new, some of it unpublished, and will open up new horizons for immunologists, endocrinologists, physiologists, cell biologists and clinicians.

Contents List of contributors........................................... ix Chapter 1 R. Dantzer, S. Laye, E. Goujan, R.-M. Bluthe, J.P. Konsman, P. Parnet and K.W. Kelley Mechanisms of action of cytokines on the central nervous system. Interaction with glucocorticoids.... Chapter 2 M.S. Harbuz and S.L. Lightman Signals from the hypothalamus to the pituitary during chronic immune responses... 15 Chapter 3 B. Kruszewska, J.A. Moynihan and D.L. Felten The role of the innervation oflymphoid tissue in the regulation of the ThllTh2 dichotomy........................... 53 Chapter 4 B.R. Walker Modulation of glucocorticoid activity by metabolism of steroids in non-lymphoid organs............................... 71 Chapter 5 J.D. Hennebold and R.A. Daynes Microenvironmental control of glucocorticoid functions in immune regulation... 101 Chapter 6 R. Foulkes, S. Shaw and A. Suitters Immunological consequences of inhibiting dehydroepiandrosterone (DHEA) sulfatase in vivo... 135 Chapter 7 F. Ramirez and D. Mason Corticosterone and the hypothalamic-pituitary-adrenal (HPA) axis in autoimmune diseases... 153 vii

viii Contents Chapter 8 D.H. Brown and B.S. Zwilling Glucocorticoid regulation of Nrampl in host resistance to mycobacteria... 169 Chapter 9 G.A.W. Rook, R. Hernandez-Pando, R. Baker, H. Orozco, K. Arriaga, L. Pavon and M. Streber Human and murine tuberculosis as models for immuno-endocrine interactions... 193 Subject Index... 221

Contributors K. Arriaga Department of Pathology, Instituto Nacional de la nutricion, Salvador Zubiran, Calle Vasco de Quiroga 15, Delegacion Tlalpan, 14000 Mexico DF R.Baker Academic Infectious Disease Unit, Department of Medicine, University College Medical School, Windeyer Building, 46 Cleveland Street, London WIP 6DB, UK R.-M. Bluthe Neurobiologie integrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France D.H.Brown Life Sciences Test Facility, U.S. Army Dugway Proving Ground, Dugway, Utah, USA R. Dantzer Neurobiologie integrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France R.A.Daynes Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Salt Lake City, Utah 84112, USA D.L. Felten Center for Psychoneuroimmunology Research and Department of Neurobiology and Anatomy, University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY 14642, USA R. Foulkes Cell tech Therapeutics, 216 Bath Street, Slough SLl 4EN, UK E. Goujon Centre G.LP. Cyceron, Boulevard Henri Becquerel, Caen, France M.S. Harbuz Department of Medicine, Bristol Royal Informary Bristol BS2 SHW, UK ix

x Contributors J.D. Hennebold Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84122, USA R. Hernandez-Pando Department of Pathology, Instituto Nacional de la nutricion, Salvador Zubiran, Calle Vasco de Quiroga 15, Delegacion Tlalpan, 14000 Mexico DF K.W.Kelley Laboratory of Immunophysiology, University of Illinois, Urbana, IL 61801, USA J.P. Konsman Neurobiologie integrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France B. Kruzewska Center for Psychoneuroimmunology Research and Department of Neurobiology and Anatomy, University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY 14642, USA S.Laye Neurobiologie integrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France S.L. Lightman Department of Medicine, Bristol Royal Infirmary, Bristol BS2 8HW, UK D.Mason MRC Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, Oxford OXI 3RE, UK J.A. Moynihan Department of Psychiatry, University of Rochester, 300 Crittenden Boulevard, Box Psych, Rochester, New York 14642, USA H. Orozco Department of Pathology, Instituto Nacional de la nutricion, Salvador Zubiran, Calle Vasco de Quiroga 15, Delegacion Tlalpan, 14000 Mexico DF P. Parnet Neurobiologie integrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France

Contributors xi L.Pavon Department of Pathology, Instituto Nacional de la nutricion, Salvador Zubiran, Calle Vasco de Quiroga 15, Delegacion Tlalpan, 14000 Mexico DF F. Ramirez MRC Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, Oxford OXI 3RE, UK G.A.W.Rook Department of Bacteriology, University College Medical School, Windeyer Building, 46 Cleveland Street, London WIP 6DB, UK S.Shaw Celltech Therapeutics, 216 Bath Street, Slough SLl 4EN, UK M.Streber Department of Pathology, Instituto Nacional de la nutricion, Salvador Zubiran, Calle Vasco de Quiroga 15, Delegacion Tlalpan, 14000 Mexico DF A. Suitters Celltech Therapeutics, 216 Bath Street, Slough SLl 4EN, UK B.R. Walker University Department of Medicine, Western General Hospital, Edinburgh EH4 2XU, UK B.Zwilling Ohio State University, Department of Microbiology, 484 West 12th Avenue, Columbus, OH43210-1292, USA