Host Defense Dysfunction In Trauma Shock And Sepsis

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.

This book contains a unique overview of the sequence of steps of host defense impairment that result from injury and lead to multiple organ dysfunction syndrome. The crucial alterations of immune and inflammatory mechanisms as they are seen during ischemia, during inter- mediate inflammatory phases, and in states of bacterial sepsis are described in detail. The role of endotoxin, its mechanisms of action, and potential counterregulatory strategies to neutralize endotoxin in order to protect from shock are discussed, as there are major etiologic factors leading to organ failure such as hepatic cellular injury and bacterial translocation. Cytokines, as the central mediators in acute phase states and the modulation of cytokine action are then evaluated carefully. In the discussion of the clinical aspects of multiple organ failure, the antibiotic interactions with host defenses, the augmentation of immunoreactivity with special nutrients and the newest insights into the regulation of wound repair are elucidated. The final sections of this book deal with therapeutic immunomodulatory approaches for the prevention ofinfections and with interventional strategies in the therapy of septic shock.

It is now well recognized that the brain, and especially the hypothalamus, plays an important role in the regulation of immune reactions and inflammation. This book aims to review our current state of knowledge of this important field. Key historical findings are presented, and the reciprocal interactions between the brain and the immune system are examined. Particular emphasis is placed on inflammation, a critical host defense reaction that serves as an effector response for both the adaptive and innate immune systems. Mechanisms implicated in brain defense, as well as in more general host defense, are discussed. The regulatory influences of the brain on inflammatory responses are included with particular reference to the role of the hypothalamus, which is also the main director the hormonal regulation of immune/inflammatory. Gender-related differences in immune responsiveness, circadian modulator of immune responses, and evidence that behavioral conditioning (e.g. reward) of immune responses is possible are used as examples to reinforce the notion that the neuroendocrine system exerts a fundamental and complex regulatory influence on the immune system. * Presents timely issues such as immunological aspects of the blood-brain-barrier and the role of inflammatory mediators in the evolution of strokes and degenerative diseases * Includes analysis of the role of the brain in the adaptive responses to disease * Evaluates the argument that further knowledge of the influence of the brain on the immune system will provide new insights to the pathophysiology infectious and autoimmune diseases

In this book, the recent developments in immunology and the impact on the treatment of infections in critical care and in surgery are presented, also describing how cellular immunology influences clinical treatment. This information helps in understanding the pathogenesis of infections in surgery and critical care. The impact of a standard treatment such as antibiotic therapy is evaluated and possible future therapy modalities outlined. This book will be of interest to clinicians and immunologists as scientists of both specialties have contributed to the book.

Severe sepsis and septic shock are the most serious compli cations of bacterial infections. Both gram-positive and gram negative bacteria can trigger these extreme inflammatory re sponses and, by so doing, cause substantial morbidity and mortality. In the United States alone, over 400 000 patients suffer from septicaemia each year, and approximately 100 000 of these patients die despite optimal intensive care and modern antimicrobial therapy. These dramatic figures have prompted intensive research to define the bacterial and host factors involved in the septic response. Scientists from many disciplines, including chem istry, physics, biology, medical microbiology, immunology, and pharmacology, have worked closely with clinicians to achieve rapid and profound progress. To translate this newly acquired knowledge into clinical practice, clinical trials have also been performed to evaluate numerous new therapeutic drugs. The disappointing results from these trials have underscored a major lesson, namely, that sepsis constitutes an extremely complex syndrome and that basic and clinical research must be greatly intensified in order to illuminate its molecular mechan isms. At this stage, the editors of the present volume of Current Topics in Microbiology and Immunology considered it would be rewarding to compile a volume summarizing our present basic and clinical knowledge on sepsis. Our particular gratitude extends to those international experts who have followed our invitation and elaborated on particular areas of the basic and clinical aspects of this field.

Inflammation in itself is not to be considered as a disease . . . and in disease, where it can alter the diseased mode of action, it likewise leads to a cure; but where it cannot accomplish that solitary purpose . . . it does mischief - John Hunter, A Treatise on the Blood, ITfIlammation, and Gunshot Woundr (London, 1794)1 As we reached the millennium, we recognized the gap between our scientific knowledge of biologic processes and our more limited clinical capabilities in the care of patients. Our science is strong. Molecular biology is powerful, but our therapy to help patients is weaker and more limited. For this reason, this book focuses on the problems of multiple organ failure (MOF), multiple organ dysfunction syndrome (MODS), and systemic inflammatory response syndrome is, patients who have severe injuries; require major, (SIRS) in high-risk patients, that overwhelming operations; or have serious illnesses requiring intensive care; patients who have diseases elsewhere, in other organs or systems, that limit their capabilities to survive a new insult; and patients who are elderly or at high risk for sepsis or other complications. These are the patients who need our help. They need the advances in science, in molecular biology, immunology, pathophysiology, biochemistry, genetics, high technology, and other areas of maximum support at the bedside. These advances could potentially have the greatest impact on improving patient care.

This textbook is written at the dawn of a new era in the management of sepsis. Recent achievements in the clinical management of septic shock are the culmination of decades of basic and applied research by innovative researchers and clinical investigators worldwide. The contributing authors to this book have spearheaded much of this research and the Editors have endeavored to create a textbook that is comprehensive in nature while maintaining a specific focus upon the multitude of work that constitutes the spectrum of sepsis research including: pathophysiology; monitoring systems; general support; microbial aspects; complications; and anti-sepsis therapies.