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.
List of Contents.- Definition and Pathogenesis of Septic Shock.- Significance and Pathogenesis of Septic Shock.- Bacterial Endotoxin: Chemical Constitution, Biological Recognition, Host Response, and Immunological Detoxification.- Superantigen-Mediated Lethal Shock: The Functional State of Ligand-Reactive T Cells.- Pathogenesis of Sepsis Syndrome: Possible Relevance of Pore-Forming Bacterial Toxins.- The Cellular Response in Sepsis.- Cytokines as Mediators in the Pathogenesis of Septic Shock.- Tumor Necrosis Factor and the Systemic Inflammatory Response Syndrome.- Mediators: Nitric Oxide and Other Toxic Oxygen Species.- Multiple Organ Failure in Septic Shock.- Involvement of Bacteria/Endotoxin Translocation in the Development of Multiple Organ Failure.- The Mechanisms of Host Defense Dysfunction Following Shock and Trauma.- Endotoxin-Based Molecular Strategies for the Prevention and Treatment of Gram-Negative Sepsis and Septic Shock.- Anticytokine Strategies for the Treatment of Septic Shock: Relevance of Animal Models.