Table Of ContentE. Faist J. L. Meakins
F. W. Schildberg (Eds.)
Host Defense
Dysfunction in Trauma,
Shock and Sepsis
Mechanisms and Therapeutic Approaches
With 416 Figures and 153 Tables
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Hong Kong Barcelona Budapest
Editors
Priv.-Doz. Dr. med. Eugen Faist
Prof. Dr. Friedrich W. Schild berg
Dept. of Surgery,
Ludwig-Maximilians-University Munich
Klinikum Grol3hadern
Marchioninistr. 15,8000 Munich 70, FRG
Jonathan L. Meakins M.D., D.Sc.
Dept. of Surgery, McGill University
Room 510.34687 Pine Avenue West
Montreal, Quebec, H3A lAl, Canada
TSBN-13: 978-3-642-77407-2 e-ISBN-13: 978-3-642-77405-8
DOl: 10.1007/978-3-642-77405-8
Library of Congress Cataloging-in-Publication Data
Host defense dysfunctions in trauma. shock, and sepsis: mechanisms and therapeutic approaches 1
Eugen Faist, Jonathan L. Meakins, F. W. Schildberg, (eds.).
Includes index.
1. Septic shock - Immunological aspects. 2. Multiple organ failure - Immunological aspects.
3. Traumatism - Immunological aspects. 4. Immunosuppression. 5. Wounds and Injuries -
immunology. I. Faist, E. (Eugen) II. Meakins, Jonathan L. III. Schild berg, F.W. (Friedrich W.)
[DNLM: 1. Immunity - physiology. 2. Infection - immunology, 3. Shock - immunology. QW
504H831] RB150. S5H67 1992 616.0T9-dc20
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Preface
This book presents a unique overview of all aspects of host defense alterations
under stressful conditions. It is based on the most important contributions given
at the "2nd International Congress on the Immune Consequences of Trauma,
Shock, and Sepsis-Mechanisms and Therapeutic Approaches," which was held
in Munich under the auspices of the most distinguished scientific societies
involved in this field (Society of Critical Care Medicine, European Society of
Intensive Care Medicine, Societe Internationale de Chirurgie, Surgical Infection
Society, Surgical Infection Society Europe, European Society for Surgical
Research, International Society for Burn Injury, American Association for the
Surgery of Trauma, and National Institutes of Health). Since the first conference
of this kind in 1988, new information from basic studies and clinical trials has
provided exciting and novel insights into the immune dysfunctions accom
panying trauma, shock, and sepsis.
The volume is divided into 18 parts presenting the structural background of
trauma-induced alterations of immune and imflammatory mechanisms as well
as the currently discussed therapeutic interventions designed to restore or
maintain normal host defenses following major injury.
Introducing the general theme of the book is a summary of the essential
keystones of trauma and sepsis-related immune deficits. Discussions of the
progress in trauma care brought through better understanding of the cell
biology of injury and of the major clinical factors that influence host defense
integrity in operative medicine provide a setting for understanding the wide
array of detailed information that is presented thereafter. The sequential steps of
host defense impairment following trauma, a phenomenon which starts within
the immediate post-trauma phase and ultimately leads to the development of
multiple organ failure (MOF) with subsequent death, are then outlined. In
dissecting the genesis of MOF, we have somewhat arbitrarily distinguished
between the phase of shock and ischemia, an intermediate inflammatory phase,
and a phase of manifest sepsis syndrome. Subsequent chapters go into the
immune pathways for controlling infection under physiologic and stressful
conditions and the inflammatory mechanisms in traumatic and septic injury,
and four parts of the book then consider the characteristics of various cytokines
and their pleiotropic functions in acute-phase states, trauma, and sepsis and
approaches to modulate cytokine actions.
VI Preface
This volume also brings up-to-date information on the effects of endotoxins,
including the massive impact of bacterial translocation on endocytosis, and on
the most recent regimens for endotoxin shock protection, including neutraliza
tion with intravenous immunoglobulins and monoclonal anti-endotoxin anti
bodies. Additional chapters consider the most recent promising immunomodu
latory approaches to both prevention and treatment of septic shock.
Updates on the mechanisms of wound healing, the role of nutrition in host
defense, clinical aspects of MOF, and antibiotic interactions with host defenses
represent further exciting topics that receive extensive discussion within this
book.
The editors are grateful to the many distinguished basic and clinical
scientists who have contributed to this book, enabling us to offer an un
paralleled breadth and depth of scientific information about the cellular mech
anisms and therapeutic approaches of host defense dysfunction in trauma,
shock, and sepsis. Only this form of integrated approach involving the many
disciplines of theoretical and clinical medicine will bring a sound conceptual
basis for the management and prevention of sepsis syndrome in the immuno
compromised host. We hope that this book will encourage and further promote
this approach.
Finally, the editors gratefully acknowledge the cooperation, tremendous
efforts, and invaluable work of three individuals who have put all their energy
into the creation of this complex book. Christian Schinkel and Svenja Zimmer,
as assistant editors, were in charge of the proofreading and the preparation of
the subject index, while Evi Gerstmeyr was responsible for the secretarial
organization related to this book and the previous congress. The editors are also
indebted to the editorial staff of Springer-Verlag for their willingness and terrific
support in preparing this book. Finally, they would like to thank Erika Hanesch
f9r the cover design.
Munich, October 1992 Eugen Faist
Jonathan L. Meakins
Friedrich W. Schild berg
Table of Contents
Section 1
General Aspects/Perspectives
Progress in Trauma Care Through Understanding the Cell Biology
of Injury
(A. E. Baue). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Trauma, Sepsis and Immune Defects
(1. A. Mannick) ............. . 15
Clinical Factors Influencing Host Defense Integrity
(1. L. Meakins) ...................... . 23
The Intensive Care Unit of Tomorrow
(H. J. Dieterich, K. Peter) ........ . 31
Section 2
Host Defense Integrity-Response and Stress
How the Immune System Discriminates Infectious Nonself
from Noninfectious Self
(c. A. Janeway Jr.) ........................ . 39
Signal Transduction Mechanisms: Pathophysiologic Alterations
(M. M. Sayeed). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Neuroendocrine Regulation of Immune Function
(J. W. Holaday, J. R. Kenner, P. F. Smith, H. U. Bryant,
E. W. Bernton). . . . . . . . . . . . . . . . . . . . . . . . . . 59
VIII Contents
Beneficial Effects of Stress Response Blockade on Patients
Undergoing Surgery
(H. Kehlet) ............................ . 67
The Impact of Preexisting Disease Conditions for Host Defense Integrity
in Traumatized and Critically III Patients
(N. V. Christou, 1. M. Tellado) . . . . . . . . . . . . . . . . . . . . . . . .. 73
Section 3
From Injury to Multiple Organ Failure:
Sequential Steps of Host Defense Impairment
3.1 Shock and Ischemia
Oxygen Radical-Mediated Endothelial Cell Injury
(G. O. Till, P. A. Ward) ........... . 85
Characteristics of Neutrophil Dysfunction
(G. F. Babcock, C. L. White-Owen, 1. W. Alexander, G. D. Warden) . 95
Endothelial Dysfunction as an Early Critical Event in Ischemia and Shock
(A. M. Lefer, X. Ma). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Role of Oxidants, Proinflammatory Agents, and Granulocytes
in the Post Ischemic Intestine
(P. Kubes, D. N. Granger) . . . . . . . . . . . . . . . . . . . . .. .... 113
Hepatic Parenchymal and Nonparenchymal Cells in Hemorrhage
and Ischemia
(M. G. Clemens) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Acute Lung Injury Following Shock and Major Trauma
(G. Schlag, H. Redl). . . . . . . . . . . . . . . . . . . . . . . . 139
Hemorrhage-Induced Alterations in Cell-Mediated Immune Function
(I. H. Chaudry, A. Ayala, D. Meldrum, W. Ertel) ............... 149
3.2 Intermediate Inflammatory Phase
Sepsis and Multiple Organ Failure: The Result of Whole Body
Inflammation
(R. 1. Goris) ..................................... 161
Contents IX
Multiple Organ Failure (MOF), and Whole Body Inflammation
After Multiple Trauma
(G. Regel, H. C. Pape, F. Koopmann, J. A. Sturm). . . . . . . .... 171
Neutrophils, Cytokines, Oxygen Radicals, and Lung Injury
(P. A. Ward, M. S. Mulligan, J. S. Warren) .................. 177
The Role of /32- Leukocyte Integrins In Vivo
(S. R. Sharar, N. B. Vedder, W. J. Mileski, C. L. Rice, J. M. Harlan,
R. K. Winn). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
The Angry Macrophage and Its Impact on Host Response Mechanisms
(R. V. Maier) .................................... 191
Eicosanoids, Cytokines and Altered Metabolic Control in the Evolution
of the Posttraumatic Host Defense Failure Syndromes (Adult Respiratory
Distress Syndrome and Multiple Organ Failure Syndrome)
(J. H. Siegel) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Diagnostic Role of New Mediators and Markers of Inflammation
in Multiple Injured Patients
(D. Nast-Kolb, Ch. Waydhas, M. Jochum, M. Spannagl, W. Machleidt,
K. H. Duswald, L. Schweiberer). . . . . . . . . . . . . . . . . . . . . . . . . 221
Intravascular Activation of Polymorphonuclear Neutrophils
in Critically III Anergic Patients
(J. M. Tellado, N. V. Christou) . . . . . . . . . . . . . . . . . . . . . . . . . 229
Mediators of Remote Lung Injury
(T. Lindsay, J. Hill, C. R. Valerie, D. Shepro, H. B. Hechtman) ...... 235
3.3 Sepsis
Immunologic Dyshomeostasis in Multiple Organ Failure:
The Gut-Liver Axis
(J. C. Marshall). . . . . . . . . . . . . . . . . . . . . . . . .. ........ 243
Tumor Necrosis Factor and Other Cytokines as Mediators
of Clinical Sepsis
(S. F. Lowry) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
The Protein C System in Septic Shock
(F. B. Taylor). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
X Contents
Leukocyte-Endothelial Interactions in Trauma and Sepsis
(H. Redl, G. Schlag, H. P. Dinges, R. Kneidinger, J. Davies) . . . . . . . . 277
Role of Oxygen Radicals in Multiple Organ Failure
(H. P. Friedl, O. Trentz, G. O. Till, P. A. Ward) . . . . ....... 287
Arachidonic Acid Metabolism in Endotoxemia and Sepsis:
Therapeutic Approaches
(1. A. Cook, E. Li, P. V. Halushka) . . . . . . . . . . . . . . . . . . . . . . . 297
Section 4
Immune Mechanisms for the Control of Infection Under Physiologic
and Stressful Conditions
Biology and Function of Cytotoxic T -Cells
(R. C. Bleackley) . . . . . . . . . . . . . . .. ................. 311
Immune Response of Heat Shock Proteins
(S. H. E. Kaufmann) ............. . . .... 317
Prostaglandins Mediate the Expression of a 72-kDa Heat Shock
Protein in Human Fibroblasts
(A. E. Heufelder, B. E. Wenzel, R. S. Bahn) . . . . . . . . . . . .. . ... 323
Glucocorticoid-Immune System Interactions in Injury and Sepsis
(S. E. Calvano) ................................... 331
Hemorrhagic Shock Inhibits Myelopoiesis Independent
of Bacterial Translocation
(D. H. Livingston, J. Hseih, T. Murphy, B. F. Rush Jr.) . . ...... 339
Monocyte HLA-DR Antigen Expression: Its Reproducibility
in Asymptomatic Volunteers and Correlation with Clinical Infection
(W. G. Cheadle, M. J. Hershman, S. R. Wellhausen, H. C. Polk Jr.). .. 349
Phenotypic and Functional Characteristics of Peripheral Blood
Lymphocytes in a Defined Group of Poly trauma Patients
(G. C. Spagnoli, M. Heberer, P. Vogel bach, R. Rosso, J. Jorgensen,
F. Harder). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .. 355
Cell-Mediated Immunity During and After Cardiopulmonary Bypass
(A. Paccagnella, S. DeAngeli, M. Mordacchini, G. Caenaro, A. Nieri,
P. Rosi, P. Michilon, M. Calo, G. Zanardo, L. Salvador,
C. Furlan, G. Simini) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
Contents XI
Alterations in Function and Phenotype of Monocytes from Patients
with Septic Disease: Predictive Value and New Therapeutic Strategies
(H. D. Volk, M. Thieme, U. Ruppe, S. Heym, W-D. Docke, D. Manger,
S. Zuckermann, A. Golosubow, B. Nieter, H. Klug, R. van Baehr) 365
Effects of Exercise on the Immune System with Special Reference
to Natural Killer Cells
(B .K. Pedersen) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
Interaction of Immune, Interferon, and Opioid Systems
in Professional Athletes
(E. Gotovtseva, I. Surkina, P. Uchakin, J. Shchurin, S. Pschenichkin,
N. Kost, A. Zozulya, O. Ilyinsky). . . . . . . . . . . . . . . . . . . . . . . . 379
Section 5
Inflammatory Mechanisms in Traumatic and Septic Injury
White Cells in Burn Patients
(D. N. Herndon, T. C. Rutan, J. Mlakar, D. Fleming) . . 385
Fibronectin Degradation: An In Vitro Model of Neutrophil Mediated
Endothelial Cell Damage
(K. D. Forsyth). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391
Adenosine Inhibits Postischemic Leukocyte Adherence to the
Endothelium of Postcapillary Venules via A -Receptor
2
(D. Nolte, H. A. Lehr, K. Messmer). . . . . . . . . . . . . . . . . . 399
Prostaglandin E] Inhibits the Stimulation of Neutrophils In Vitro and
In Vivo and Improves Cardio-Respiratory Functions in Multiply
Traumatized Patients at Risk of Adult Respiratory Distress Syndrome
(A. Dwenger, M. L. Nerlich, E. Jonas, G. Schweitzer, J. A. Sturm,
H. Tscherne) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403
Production and ,Characterization of Peptide-Specific Monoclonal
Antibodies that Recognize a Neoepitope on Hog C5a
(u. Hopken, A. Striiber, M. Oppermann, M. Mohr, K. H. Miicke,
H. Burchardi, O. Gotze) . . . . . . . . . . . . . . . . . . . . . . .. . ... 411
The Oxidative Burst Reaction of Neutrophils is Reduced by the
Acute Phase Serum Amyloid-A Protein
(R. P. Linke, V. Bock, G. Valet, G. Rothe) ................... 419
