Cytokines and the CNS

363 Pages·2005·15.846 MB·English

by  Richard M. Ransohoff, Etty N. Benveniste

Second Edition
CY TOK INES
and the
CNS
Copyright © 2006 Taylor & Francis Group, LLC
Second Edition
CY TOK INES
and the
CNS
Edited by
Richard M. Ransohoff
Etty N. Benveniste
Boca Raton London New York
A CRC title, part of the Taylor & Francis imprint, a member of the
Taylor & Francis Group, the academic division of T&F Informa plc.
Copyright © 2006 Taylor & Francis Group, LLC
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Published in 2006 by
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© 2006 by Taylor & Francis Group, LLC
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International Standard Book Number-10: 0-8493-1622-7 (Hardcover)
International Standard Book Number-13: 978-0-8493-1622-7 (Hardcover)
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Library of Congress Cataloging-in-Publication Data
Cytokines and the CNS / edited by Richard M. Ransohoff, Etty Benveniste.--2nd ed.
p. cm.
Includes bibliographical references and index.
ISBN 0-8493-1622-7
1. Neuroimmunology. 2. Cytokines. I. Ransohoff, Richard M. II. Benveniste, Etty N.
QP356.47.C96 2005
616.8'0479--dc22 2005046283
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Dedication
I dedicate this book to my wife, Margaret S. Ransohoff, to
my children, Amy and Lena Ransohoff, and to my parents,
Sue and Jerry Ransohoff.
Richard Ransohoff
This book is dedicated to my mother, Oro Benveniste.
Etty Benveniste
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Preface
It has been almost exactly 10 years since we began work on the first edition of this
book. We were strongly motivated by the explosive growth in knowledge about
cytokines/chemokines and cytokine/chemokine signaling, and the potential for appli-
cation of this information to understanding the development, physiology, and pathology
of the central nervous system (CNS). Our efforts were gratified by considerable
interest in the book, which remains in print today (selling three units in the first half
of 2004). Using the prosaic descriptor afforded by counting PubMed citations
(“Cytokines” AND “Central Nervous System”), there were 2225 papers in this field
during more than 28 years captured in the current PubMed index (from 1966 to
September 1994), with less than 1000 in the period 1966–1989 and 1244 (56%)
appearing in the five years before our first edition (1989–1994). Indeed, the MESH
entries for “cytokine” (1991) and “cytokine receptor” (1994) were then still newly-
minted. Since then, the pace has only accelerated, with another 6189 papers (74%
of all articles on the subject) in the past 10 years, meaning that, during the past
decade, every 18 months brought on average as many reports in this field as in the
first 23 years.
The first edition was organized to present information that would serve overlap-
ping purposes for neurobiologists, immunobiologists, and other interested parties.
Basic cytokine biology (receptors, signaling, cellular responses) took up the first
three chapters, with the fourth devoted to introducing the unique cellular elements
of the CNS. Three chapters addressed how these CNS cells respond to cytokine
stimulation, with the last six addressing how cytokine interactions play out in the
setting of CNS pathology.
When preparing the first edition, our feeling was that cytokine biology needed
an introduction to neurobiologists for two reasons: (1) receptor structure and post-
receptor signaling had achieved a level of coherence and mechanistic detail that
could be readily communicated; and (2) there was enough similarity (at times identity)
between factors involved in inflammation or immunity and those implicated in neural
development, physiology, and repair that familiarity with cytokines was an essential
element in the neurobiologist’s cognitive tool kit. Conversely, for immunobiologists,
the concepts elaborated on by neurobiologists to understand developmental pattern-
ing and networked organ function were so elegant that comprehension of cytokine
action in the CNS could only enhance appreciation of ways the immune system
might work. These principles remain unaltered. The design of this second edition
embraces three chapters on basic cytokine biology, following one chapter on the
CNS (cells, tissues, basic pathological reactions to insult). Next are four chapters
that integrate cytokine biology into basic CNS processes (development, inflamma-
tion, immunity, degeneration/repair). There are five chapters that apply this body of
knowledge to disease or pathology (neurodegeneration, neoplasia, multiple sclerosis,
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trauma, infection). Finally, we look forward in a last chapter to the translation of
cytokine biology to treatment, an entirely new and welcome topic.
Fortunately, the organizing concepts for the first volume remain largely valid.
We put forth that the newly-proposed notion of grouping cytokines according to
receptor structure would be enduringly useful, and the groups I and II cytokine
receptors were presented as illustrative examples. The ongoing utility of this
approach can be deduced from following the expanding (but not exploding) field of
interleukins. Our first volume indexed 10 interleukins; there are now at least 29.
Reassuringly, the newer interleukins fall into families defined by older members (for
example, IL-22, IL-24, IL-26, IL-28 and IL-29 are members of the IL-10 family;
IL-23 is a member of the IL-12 family; IL-25 is a member of the IL-17 family; and
IL-27 is an IL-6 family member), forestalling a bit of ‘shock of the new.’ Remarkably,
the families remain functionally defined, as proposed more than a decade ago, by
shared receptor subunit utilization. Challenges to usable core memory remain, how-
ever: Online Mendelian Inheritance in Man (OMIM) lists no less than 18 TNF
superfamily ligands (TNFSFs), signaling to 25 receptors (TNFSFRs). This nomen-
clature has been adopted haltingly and spottily, making the relevant literature dense
for the casual user. Nevertheless, the critical importance of this group of molecules
for neuroimmunology (comprising components such as the p75/LNGFR in addition
to TNF, its receptors; Fas and FasL; CD154 and CD40) dictates that the effort must
be made. Ready availability of Web-based resources is a welcome aide memoire,
growing at about the same pace as new nomenclatures and molecules.
The current edition of Cytokines and the CNS is therefore continuous with its
predecessor. However, in another sense, it is entirely original, since each chapter
was prepared by a new contributor. This evolutionary change was not dictated by
any one of the previous authors leaving the field, but rather by our desire to have a
fresh look at each topic. The chapters of this second edition cover much of the same
ground as previously, but focus more on processes (immunity, inflammation, devel-
opment) than individual cell types (oligodendroglia, astrocytes; neurons). The major
pathological processes that concern us today (infection, trauma, neurodegeneration;
multiple sclerosis) are those discussed previously. We are endlessly grateful to our
contributors, whose scholarship and hard work were continuously amazing, and hope
that their efforts translate seamlessly to benefit for readers. The advance of knowl-
edge in these fields will be apparent to cursory comparison of the first and second
editions. Tasks that remain undone are formidable indeed: foremost among them is
to understand how cells and tissues integrate simultaneous or sequential multiple
cytokine signals to produce biological outcomes. These types of questions demand
new methods of analysis, for which the very first drafts have only recently been
described. We hope that the biology described in the current book helps to persuade
the contemporary and future community of CNS/cytokine researchers that the goal
is worth the effort.
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Editors
Etty (Tika) Benveniste is professor and chairman of the Department of Cell Biology
at the University of Alabama at Birmingham. She received her Ph.D. in immunology
from the University of California, Los Angeles, in 1983, and was a postdoctoral
fellow in the laboratory of Dr. Jean Merrill, Department of Neurology, UCLA, from
1983 to 1986.
Dr. Benveniste has received numerous honors and awards, including NIH Train-
ing Grant Fellowships (1982–1983, 1984–1985); a postdoctoral fellowship award
from the National Multiple Sclerosis Society (1986–1987); Plenary Lecturer, Fourth
International Congress of Neuroimmunology (1994); Plenary Lecturer, UCLA Neu-
robiology of Disease Conference (1995); Member and Plenary Lecturer, Sixth Inter-
national Congress on TNF and Related Cytokines (1996); Distinguished Scientist
Lecturer, University of Arkansas (1998); Keynote Speaker, Great Lakes Glia Meeting
(1999); Chair, FASEB Summer Conference, Neural-Immune Interactions (2000,
2002); Symposium Speaker, Oklahoma Center for Neuroscience (2003); and Exec-
utive Chair, NIH Workshop on Glial Inflammation (2003).
Dr. Benveniste has served on numerous review and advisory boards. These
include Member, NIH Special Section for AIDS and Related Research Review Group
(1998–1991); Member, American Cancer Society: Advisory Committee for Cell
Biology (1992–1995); Member, NIH Neurosciences Program Project Review Com-
mittee B (1993–1995); Chair, NIH Neurosciences Program Project Review Commit-
tee B (1995–1997); External Advisory Board, Center for Neurovirology, University
of Nebraska Medical Center (1997–present); Member, National Multiple Sclerosis
Society Grant Review Committee (1998–2003); Member, NIH Training Grant and
Career Development Review Committee (1999–2002); Member; NIH Clinical Neu-
roimmunology and Brain Tumors (2000–2004); Member, Sontag Foundation Scien-
tific Advisory Board (2003–present); Member, National Multiple Sclerosis Society,
Research Programs Advisory Committee (2004–present); Chair, NIH Clinical Neu-
roimmunology and Brain Tumors (2004–present); and Member, Oklahoma Medical
Research Foundation Board of Scientific Visitors (2004–present). She is a member
of the Editorial Boards of the Journal of Biological Chemistry, Journal of Neuro-
science, GLIA, Journal of Neuroimmunology, and Journal of Neurovirology.
For the past 18 years, Dr. Benveniste’s research has focused on the function of
cytokines and signal transduction pathways operative in glial cells, and their con-
tributions to CNS disease. Dr. Benveniste has received continuous research support
from the NIH, NMSS, and AmFAR since 1988. She has published over 150 scientific
reports and reviews, numerous book chapters, and edited two books.
Dr. Benveniste is a member of the International Society of Neuroimmunology,
the American Society for Neurochemistry, the American Association of Immunolo-
gists, the Society for Neuroscience, and the American Society of Cell Biology.
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Dr. Benveniste is married to Dr. Casey Morrow, and they have one son, Jackson
Morrow (12).
Richard M. Ransohoff is professor of molecular medicine at the Cleveland Clinic
Lerner College of Medicine, a staff scientist in the Department of Neurosciences of
the Lerner Research Institute, and a staff neurologist in the Mellen Center for MS
Treatment and Research, both at the Cleveland Clinic Foundation (CCF), Cleveland,
Ohio. He is also a professor of pathology (Adjunct) at Case Medical School. Dr.
Ransohoff graduated with honors from Bard College, Annandale, New York, with a
B.A. in literature and received the M.D. degree with honors from Case School of
Medicine, Cleveland, Ohio. He completed residencies in internal medicine (Mt. Sinai
Medical Center, Cleveland, Ohio; Board Certified 1981) and neurology (CCF; Board
Certified 1985). From 1984 to 1989, Dr. Ransohoff was a postdoctoral fellow in the
laboratory of Dr. Timothy Nilsen, Department of Molecular Biology and Microbi-
ology, Case School of Medicine.
Among other honors and awards, he received a Physician’s Research Training
Award from the American Cancer Society (1984–1986); a Harry Weaver Neuro-
science Scholarship from the National Multiple Sclerosis Society (NMSS;
1987–1992); a Clinical Investigator Development Award from the National Institutes
of Health (NIH; 1988–1993); a Heritage Scholar at the University of Alberta (1998);
Distinguished Lecturer at the University of Arkansas School of Medicine (2002); a
recipient of the John and Samuel Bard Award in Science and Medicine (2002); and
a speaker at the American Academy of Neurology’s Plenary Symposium “Frontiers
in Clinical Neuroscience” in 2004. He has been cited from 1996 through the present
(2004) in the Best Doctors in America for his expertise in the clinical care of patients
with multiple sclerosis (MS).
Dr. Ransohoff served as a regular member on NIH and National Multiple Scle-
rosis Society (NMSS) Study Sections; on numerous Special Emphasis Panels; and
as Chair of the NMSS Peer Review Committee B from October 2004. He is a member
of the editorial boards of The Journal of Immunology (where he is presently Section
Editor); Trends in Immunology; Current Immunology Reviews, and the Journal of
Neuroimmunology. From 1998 to 2000, Dr. Ransohoff was a member of the NINDS
Director's Planning Panel on “The Neural Environment.” He is a member of the
Steering Committee for the NIH/NINDS Spinal Muscular Atrophy Project; the
International Advisory Boards for the 7th (2004) and 8th (2006) Congresses on
Neuroimmunology; and the Scientific Advisory Board for Chemocentryx, San Car-
los, California. He serves on External Advisory Boards for CHARTER (CNS HIV
Anti-Retroviral Therapy Effects Research; MH22005); a Program Project on Alex-
ander’s Disease (NS 42803); the MS Lesion Project (NMSS RG 3185); the Univer-
sity of Nebraska’s Center for Neurovirology & Neurodegenerative Disorders
(NS43985) and is the External Advisor for the European Union’s Project on ‘Mech-
anisms of Brain Inflammation” (QLG3-00612). He is a member of the National MS
Society’s Medical Advisory Board. He is a Co-director of the Marine Biological
Laboratory’s special topics course on “Pathogenesis of neuroimmunological disease”
held biennially at Wood’s Hole, Massachusetts.
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For the past decade, Dr. Ransohoff’s research has focused on the functions of
chemokines and chemokine receptors in development and pathology of the nervous
system. He also has a longstanding and continuing interest in the mechanisms of
action of interferon-beta. Dr. Ransohoff has received continuous research support
from the NIH and the NMSS since 1988. He has published more than 130 scientific
reports, more than 35 reviews and book chapters, and three edited books.
Dr. Ransohoff is a member of the American Academy of Neurology, the Amer-
ican Neurological Association, the American Association for the Advancement of
Science, and the American Association of Immunologists.
Dr. Ransohoff is married to Margaret Ransohoff. They have two daughters, Amy
(14) and Lena (10).
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Contributors
Wendy Smith Begolka Donald L. Durden
Northwestern University Emory University School of Medicine
Feinberg School of Medicine Atlanta, Georgia, USA
Chicago, Illinois, USA
Limin Gao
Case Western Reserve University
John R. Bethea
Cleveland, Ohio, USA
University of Miami
School of Medicine
Georges E. Grau
Miami, Florida, USA
Université de la Méditerranée
Aix-Marseille II, France
Valerie Bracchi-Ricard
University of Miami Reinhard Hohlfeld
School of Medicine Ludwig Maximilians University
Miami, Florida, USA Munich, Germany
Roberta Brambilla Sunhee C. Lee
University of Miami Albert Einstein College of Medicine
School of Medicine Bronx, New York, USA
Miami, Florida, USA
Margot Mayer-Pröschel
University of Rochester Medical Center
Celia F. Brosnan
Rochester, New York, USA
Albert Einstein College of Medicine
Bronx, New York, USA
Eileen J. McMahon
Northwestern University Feinberg
Valéry Combes
School of Medicine
Université de la Méditerranée
Chicago, Illinois, USA
Aix-Marseille II, France
Erwin G. Van Meir
Melissa A. Cosenza Emory University School of Medicine
Albert Einstein College of Medicine Atlanta, Georgia, USA
Bronx, New York, USA
Robert H. Miller
Michael David Case Western Reserve University
University of California San Diego Cleveland, Ohio, USA
La Jolla, California, USA
Stephen D. Miller
Nandini Dey Northwestern University
Emory University School of Medicine Feinberg School of Medicine
Atlanta, Georgia, USA Chicago, Illinois, USA
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