The Hypothalamus-Pituitary-Adrenal Axis

389 Pages·2007·5.442 MB·1-394\389

by  Adriana del Rey, George P. Chrousos and Hugo O. Besedovsky (Eds.)

Neuroimmune Biology
Series Editors
I. Berczi, A. Szentivanyi
Advisory Board
B.G. Arnason, Chicago, IL M.D. Kendall,Cambridge, UK
E. Arzt, Buenos Aires,Argentina E.A. Korneva, St.Petersburg,Russia
P.J. Ba`rnes,London,UK K.Kovacs,Toronto,Canada
T. Bartfai, La Jolla, CA G.Kunkel, Berlin, Germany
L. Berto´k, Budapest, Hungary L.A. Laitinen, Helsinki, Finland
H.O. Besedovsky, Marburg, Germany B. Marchetti,Catania, Italy
J. Bienenstock,Hamilton, Canada L. Matera, Turin, Italy
C.M. Blatteis, Memphis,TN H.Ovadia, Jerusalem,Israel
J. Buckingham, London, UK C.P. Phelps,Tampa, FL
Ch. Chawnshang, Rochester,NY L.D. Prockop, Tampa,FL
R. Dantzer, Bordeau, France R. Rapaport,New York,NY
M. Dardenne,Paris, France S. Reichlin, Tucson, AZ
N.Fabris,Ancona, Italy R. Schmidt,Hannover, Germany
R.C. Gaillard, Lausanne, Switzerland A.Shmakov, Novosibirsk,Russia
Ch. George, Bethesda, MD K.Skwarlo-Sonta, Warsaw, Poland
R. Good, Tampa, FL E.M. Sternberg,Bethesda,MD
R.M. Gorczynski, Toronto, Canada D.W. Talmage, Denver, CO
C. Heijnen,Utrecht,The Netherlands S. Walker,Columbia, MO
T. Hori, Fukuoka, Japan A.G. Zapata, Madrid, Spain
H.Imura, Kyoto, Japan
The Hypothalamus–Pituitary–Adrenal
Axis
Volume Editors
Adriana del Rey
Institute of Physiology
University of Marburg
Marburg, Germany
George P. Chrousos
University of Athens
Athens, Greece
Hugo O. Besedovsky
Institute of Physiology
University of Marburg
Marburg, Germany
AMSTERDAM(cid:2)BOSTON(cid:2)HEIDELBERG(cid:2)LONDON(cid:2)NEWYORK(cid:2)OXFORD
PARIS(cid:2)SANDIEGO(cid:2)SANFRANCISCO(cid:2)SINGAPORE(cid:2)SYDNEY(cid:2)TOKYO
Elsevier
Radarweg29,POBox211,1000AEAmsterdam,TheNetherlands
LinacreHouse,JordanHill,OxfordOX28DP,UK
Firstedition2008
Copyright(cid:2)2008ElsevierB.V.Allrightsreserved
Nopartofthispublicationmaybereproduced,storedinaretrievalsystem
ortransmittedinanyformorbyanymeanselectronic,mechanical,photocopying,
recordingorotherwisewithoutthepriorwrittenpermissionofthepublisher
PermissionsmaybesoughtdirectlyfromElsevier’sScience&TechnologyRights
DepartmentinOxford,UK:phone(þ44)(0)1865843830;fax(þ44)(0)1865853333;
email:[e-mail]tyourrequestonlineby
visitingtheElsevierwebsiteathttp://www.elsevier.com/locate/permissions,andselecting
ObtainingpermissiontouseElseviermaterial
Notice
Noresponsibilityisassumedbythepublisherforanyinjuryand/ordamagetopersons
orpropertyasamatterofproductsliability,negligenceorotherwise,orfromanyuse
oroperationofanymethods,products,instructionsorideascontainedinthematerial
herein.Becauseofrapidadvancesinthemedicalsciences,inparticular,independent
verificationofdiagnosesanddrugdosagesshouldbemade
LibraryofCongressCataloging-in-PublicationData
AcatalogrecordforthisbookisavailablefromtheLibraryofCongress
BritishLibraryCataloguinginPublicationData
AcataloguerecordforthisbookisavailablefromtheBritishLibrary
ISBN: 978-0-444-53040-0
ISSN: 1567-7443
ForinformationonallElsevierpublications
visitourwebsiteatelsevierdirect.com
PrintedandboundinU.K.
08 09 10 11 12 10 9 8 7 6 5 4 3 2 1
Working together to grow
libraries in developing countries
www.elsevier.com | www.bookaid.org | www.sabre.org
vii
List of Contributors
Matias Acun˜a
Laboratorio de Fisiolog´ıa yBiolog´ıa Molecular,DepartamentodeFisiolog´ıa,
Biolog´ıa Moleculary Celular, Facultad deCiencias Exactasy Naturales,
Universidad de Buenos Aires, Ciudad Universitaria, Pabello´n II,
C1428EHA, Buenos Aires,Argentina
Eduardo Arzt
Laboratorio de Fisiolog´ıa yBiolog´ıa Molecular,DepartamentodeFisiolog´ıa,
Biolog´ıa Moleculary Celular, Facultad deCiencias Exactasy Naturales,
Universidad de Buenos Aires, Ciudad Universitaria, Pabello´n II,
C1428EHA, Buenos Aires,Argentina
Peter J. Barnes
DepartmentofThoracicMedicine,National Heart and Lung Institute,
Dovehouse Street, London, SW36LY,UK
AlbertusBeishuizen
DepartmentofIntensiveCare, VU University Medical Center,
De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
Hugo O.Besedovsky
DepartmentofImmunophysiology, Institute ofPhysiology and Pathophysiology,
Medical Faculty, 35037Marburg, Germany
StefanR. Bornstein
III Medical Clinic, University Hospital Carl Gustav Carus, atthe Technical
University ofDresden, Fetscherstrasse 74 01307 Dresden, Germany
CarolinaP. Castro
Laboratorio de Fisiolog´ıa yBiolog´ıa Molecular,DepartamentodeFisiolog´ıa,
Biolog´ıa Moleculary Celular, Facultad deCiencias Exactasy Naturales,
Universidad de Buenos Aires, Ciudad Universitaria, Pabello´n II,
C1428EHA, Buenos Aires,Argentina
George P. Chrousos
FirstDepartment ofPediatrics, Aghia SophiaChildrens Hospital,University ofAthens,
Athens, Greece
viii ListofContributors
John A.Cidlowski
NIEHS, 111 T.W.Alexander Dr. Building 101, Room F-354,
Research Triangle Park,Durham, NC 27709,USA
Firdaus S. Dhabhar
DepartmentofPsychiatry, Program inImmunology &Cancer Center,
StanfordUniversity, GrantBuilding, Lab S-207, 300 PasteurDrive,
MC 5135, Stanford, CA 94305-5135, USA
Adrian J. Dunn
PacificBiosciencesResearchCenterandDepartmentofPsychology,UniversityofHawaii
at Manoa Honolulu, Hawaii, USA
Ilia J.Elenkov
Institute ofNeurobiology and Molecular Medicine, Italian National ResearchCouncil,
Via Fosso del Cavaliere100, 00133 Rome,Italy
Denis P. Franchimont
Division ofGastroenterology,Montreal General Hospital, McgillUniversity, Montreal,
Canada
Damiana Giacomini
Laboratorio de Fisiolog´ıa yBiolog´ıa Molecular,DepartamentodeFisiolog´ıa,
Biolog´ıa Moleculary Celular, Facultad deCiencias Exactasy Naturales,
Universidad de Buenos Aires, Ciudad Universitaria, Pabello´n II,
C1428EHA, Buenos Aires,Argentina
Paul M.Guyre
DepartmentofPhysiology, Dartmouth Medical School,Lebanon NH 03756-0001, USA
Peter Ha¨rle
DepartmentofInternal Medicine I,University Hospital Regensburg,
93042 Regensburg, Germany
Klaus Heeg
Dept.ofHygiene and Medical Microbiology, University ofHeidelberg,
Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
Carmen Herna´ndez-Lo´pez
Centre for Microscopy and Cytometry,Complutense University, 28040 Madrid, Spain
David Janele
DepartmentofInternal Medicine I,University Hospital Regensburg,
93042 Regensburg, Germany
WilfridJa¨nig
Physiologisches Institut, Christian-Albrechts-Universita¨tzu Kiel,
Olshausenstr.40, Olshausenstr. 40,Germany
ListofContributors ix
Eva Jime´nez
DepartmentofCellBiology,FacultyofMedicine,ComplutenseUniversity,28040Madrid,
Spain
T. Bucky Jones
TheOhioStateUniversity,CollegeofMedicine,CenterforBrainandSpinalCordRepair,
460 W. 12th Avenue, 786Biomedical Research Tower, Columbus, Ohio 43210, USA
MartinKees
DepartmentofInternal Medicine I,University Hospital Regensburg,
93042 Regensburg, Germany
Alexander W. Krug
Medical Clinic III, Carl Gustav Carus University Hospital,
University ofDresden, Dresden,Germany
Ivan Lefkovits
ResearchDepartmentoftheUniversityClinics,PhysiologyInstituteofUniversityofBasel,
Vesalianum, Vesalgasse 1,CH-4051 Basel, Switzerland
Kurt M. Lucin
DepartmentofNeurologyandNeurologicalSciences,StanfordUniversity School of
Medicine,300PasteurDrive, Rm 343, MC 5235, Stanford, CA 94305, USA
Jeanette I. Webster Marketon
Institute for Behavioral Medicine Research and Divisionof Pulmonary,Allergy,
Critical Careand Sleep Medicine,Department ofInternal Medicine,
TheOhio State University, 2058A Graves Hall, 333 W.10th Ave,
Columbus, OH43210,USA
Allan Munck
EmeritusDepartmentofPhysiology,DartmouthMedicalSchool,LebanonNH03756-0001,
USA
Juan J. Mun˜oz
Centre for Microscopy and Cytometry,Complutense University, 28040 Madrid, Spain
AlbertoC. Nagashima
Laboratorio de Fisiolog´ıa yBiolog´ıa Molecular,DepartamentodeFisiolog´ıa, Biolog´ıa
Molecular yCelular, Facultadde Ciencias Exactas yNaturales, Universidad deBuenos
Aires,Ciudad Universitaria, Pabello´n II, C1428EHA, Buenos Aires, Argentina
Marcelo Pa´ez-Pereda
Max-Planck InstituteofPsychiatry, Kraepelinstr. 10, 80804 Munich, Germany
Louis DuPasquier
InstituteofZoologyandEvolutionaryBiology,Vesalgasse1,CH-4051Basel,Switzerland
Georg Pongratz
DepartmentofInternal Medicine I,University Hospital Regensburg,
93042 Regensburg, Germany
x ListofContributors
PhillipG. Popovich
TheOhio State University, College ofMedicine,Center for Brain
and SpinalCord Repair,460 W. 12th Avenue, 786Biomedical Research Tower,
Columbus, Ohio43210,USA
Ulrich Renner
Max-Planck InstituteofPsychiatry, Kraepelinstr. 10, 80804 Munich, Germany
Adriana del Rey
Institute ofPhysiology, University ofMarburg,Marburg, Germany
Rosa Sacedo´n
DepartmentofCell Biology,Faculty ofMedicine,Complutense University,
28040 Madrid,Spain
Ju¨rgen Scho¨lmerich
DepartmentofInternal Medicine I,University Hospital Regensburg,
93042 Regensburg, Germany
Kathleen A.Smoak
Laboratory ofSignal Transduction, National Institute ofEnvironmental Health Sciences,
DepartmentofHealthand Human Services, National Institutes ofHealth,
Research Triangle Park,North Carolina 27709, USA
Gu¨nter K.Stalla
Max-Planck InstituteofPsychiatry, Kraepelinstr. 10, 80804 Munich, Germany
Esther M.Sternberg
SectiononNeuroendocrineImmunologyandBehavior,NationalInstituteofMentalHealth,
National Institutesof Health, Department of Health and Human Services, 36, Convent
Drive MSC-4020,Bldg 36, Room 1A23,Bethesda,MD 20892-4020, USA
Rainer H.Straub
Laboratory ofNeuroendocrinoimmunology,Dept.ofInternal Medicine I,
University Hospital,93042 Regensburg, Germany
AlbertoVaras
DepartmentofCell Biology,Faculty ofMedicine,Complutense University,
28040 Madrid,Spain
HelmutVedder
DepartmentofGeneral Psychiatry,Psychotherapy and Psychosomatics II Nordbaden
Psychiatric Centre,Heidelberger Strasse 1a, 69168Wiesloch, Germany
Istvan Vermes
DepartmentofClinicalChemistry, Medical Spectrum Twente, Hospital Group,
P.O.Box 50000, 7500KA Enschede,The Netherlands
ListofContributors xi
Angeles Vicente
DepartmentofCell Biology,Faculty ofMedicine,Complutense University,
28040 Madrid,Spain
Ilias Vrezas
DepartmentofEndocrinology, University Hospital ofDuesseldorf,
Moorenstr. 5 40225, Duesseldorf,Germany
Mark P. Yeager
Dartmouth Medical School, Lebanon NH03756-0001, USA
Agust´ın G.Zapata
DepartmentofCell Biology,Faculty ofBiology, Complutense University,
28040 Madrid,Spain
ChristianG.Ziegler
MedicalClinicIII,CarlGustavCarusUniversityHospital,UniversityofDresden,
Dresden,Germany
xiii
Foreword
Studiesoninteractionsbetweentheimmune,endocrine,andnervoussystemscannolongerbe
consideredasanemergingfieldinbiologicalandmedicalsciences.Indeed,inthelast30years,
hundreds of publications dealing with different aspects of this field appeared in prestigious
multidisciplinary journals and in journals specialized in immunology, endocrinology, and
neurosciences. As it usually occurs, the development of a scientific field is preceded by a
stage that can be called ‘‘prehistory,’’ in which few primitive facts serve for claims that are
not based on scientifically structured hypotheses and concepts. We have to admit that the
‘‘prehistoric’’ period in the field of immune–neuroendocrine interactions was a little bit too
long, in which holistic statements such as ‘‘the brain and the mind control everything and
then ... whynottheimmunesystem?’’predominated.Furthermore,theexperimentalevidence
available at that time often derived from a primitive technology or from studies restricted to
non-adaptive acute hypersensitivity and anaphylactic reactions. The most solid evidence of
endocrineeffectsonimmunitywasthatadrenocorticalhormonesareanti-inflammatoryandcan
affectimmuneorgansandthedistributionoflymphoidcells.SuchknowledgeledHansSelyeto
predictthatstresscaninfluenceimmuneprocess,apredictionthatisatpresentfullyconfirmed
and continuestobe investigatedin detail.
Since then, an enormous bulk of information has accumulated indicating that the immune
and neuroendocrine systems interact and control each other. Unfortunately, for some time,
most immunologists were reluctant to accept the existence of a level of neuroendocrine
control of immune processes. Retrospectively, this reluctancy is easy to justify since, at that
time, it was still necessary to elucidate crucial intrinsic immune mechanisms. The main
concern of immunologists was to understand the immune system from ‘‘within,’’ with a
tendency to ignore that immune cells are also exposed to external signals that affect the
system. To look ‘‘inside’’ the immune system yielded formidable results. Now, the structure
of the main molecules (e.g., antibodies, T-cell receptor) that recognizes the huge universe of
antigens is known. The molecular and genetic bases of the differentiation and diversification
of immune cells as well as the types and subtypes of cells that participate in an immune
response are largely understood. The biochemical pathways of immune cell activation and
how these cells interact and receive information from antigen-presenting cells have also been
clarified to a great extent. This knowledge showed that immune cells are extremely complex,
and that refined interactions between them constitute the basis of different types of immune
responses.
The identification of efficient autoregulatory mechanisms may suggest that, compared to
other physiologic systems, the immune system displays a privileged autonomy. However, a
physiological immune response in an organism depends on mechanisms that are under neuro-
endocrinecontrol.Themostobviouslevelofsuchdependenceistheneedtocontrolthehighly
xiv Foreword
demanding metabolic processes that underlie immune cell functions. Another example of
dependence is relatedto the circulatorysystems. Indeed, no effective immune response would
be possible if immune cells could not circulate and reach the places where antigens are
presented.
Hormones, neurotransmitters, and neuropeptides can also influence more refined mechanisms
underlyingimmunecellactivity.Immunecellsperforminanenvironmentwherealltheseagentsare
presentandcanperceiveneuroendocrinesignalsviaspecificreceptors.Thereisclearevidencethat
immunecellscanestablishclosecontactswithnervefibersbothinlymphoidorgansandintissues
wheretheymeetandrecognizeantigens,andexpandanddevelopaseffectorcells.Itisalsoknown
thatcertainimmuneproductsandsomehormonesandneurotransmittersshearsecondintracellular
messengers, transcription factors, and post-transcriptional mechanisms, a situation that allows a
mutualmodulationoftheireffectsatintracellularlevels.Ontheotherhand,differenttypesofimmune
cellsexpressadifferentnumberofreceptorsforagivenneuroendocrineagentandthisnumbervaries
afteractivation.Thus,thedistinctsensitivityofrestingandactivatedcellstotheseagentscontributes
toimmunospecificityandallowsaneuroendocrinecontrolofdefinedstepsoftheimmuneresponse.
It is important to remark here that, under natural conditions, hormones, neurotransmitters, and
neuropeptides represent the efferent messengers of complex immune–neuroendocrine regulatory
circuits.Indeed,aswithothersystemsunderneuroendocrineregulation,theimmunesystemconveys
signalstocentralregulatoryagenciesthatinturnrespondandaffectthecourse,development,and
terminationoftheimmuneresponse.Thefirstneuroendocrineimmunoregulatorycircuitwaspostu-
lated when it was shown that, following antigenic challenge, immune cell products stimulate the
hypothalamus–pituitary–adrenal(HPA)axisandthattheresultingincreaseinglucocorticoidoutput
can affect the immune response. The organization of this circuit and its relevance for health and
diseaseisthemaintopicofthisvolume.
The first chapter (A. Dunn) provides a general perspective of the content of this volume.
Then,weconsidereditusefultoofferananatomicalandphysiologicaldescriptionoftheHPA
axis (H. Vedder) and an analysis of how glucocorticoids can signal during health and disease
(K.SmoakandJ.Cidlowski).Becauseofitscomplementaryphysiologicalfunctioningwiththe
HPA axis, the organization of the sympathetic nervous system is included (W. Ja¨nig). Also a
briefdescriptionoftheinnate(K.Heeg)andspecific(I.LefkovitsandL.DuPasquier)immune
responses, as well as how the immune system functions in the brain (T. Jones, K. Lucin, and
P.Popovich),ispresented.Thesecondpartofthisvolumeisdevotedtoeffectsandmechanisms
of action of glucocorticoids on immune processes (P. Guyre, M. Yeager, and A. Munck),
including their effects on the developing thymus (R. Sacedo´n et al.). The action of catechol-
amines (I. Elenkov) on immunity and the dual suppressive and enhancing effects of stress on
immunefunction(F.Dhabhar)arealsocoveredinthispart.Thethirdpartofthisvolumedeals
with afferent signalsdeliveredtothe brain,endocrineglands,andtheautonomic nervesystem
duringimmuneresponses.HowimmunesignalsareprocessedatbrainlevelandaffecttheHPA
axis(H.BesedovskyandA.delRey),andtheeffectofinflammatorymediatorsonthepituitary
(D. Giacomini et al.), the adrenal glands (I. Vrezas et al.), and the autonomic nervous system
(R. Straub et al.) are addressed here. The last part covers the clinical relevance of HPA axis–
immune interactions, particularly during sepsis and the multiple organ dysfunction syndrome
(I. Vermes and A. Beishuizen) and inflammatory disorders (J. Webster Marketon and
E. Sternberg). The development of glucocorticoid resistance during inflammatory diseases
(D. Franchimont and G. Chrousos) and the role of glucocorticoids in asthma (P. Barnes) are
also discussed.
We hope that this volume provides a comprehensive view of the molecular and functional
organization oftheimmune–HPAaxiscircuitanditsclinicalrelevance.We alsoexpectthatit