Sepsis: rethinking the approach to clinical research

Abstract: The clinical syndrome of sepsis encom-passes a highly heterogeneous group of clinical disorders, varying with respect to the site, bacteri-ology, and even presence of infection and with the clinical syndrome evolving in the host. Clinical tri-als of strategies to modulate the host response that mediates sepsis were first initiated 25 years ago. A continuing record of disappointment has charac-terized subsequent work, and only a single new therapy has been licensed for clinical use. Yet, these commercial disappointments obscure a vi-brant body of new knowledge that has clarified the biology of the innate immune response whose de-ranged expression is responsible for sepsis and that has provided important new insights into the fail-ings of the traditional model of clinical research in sepsis. This review highlights advances in basic bi-ology and underlines insights from clinical re-search that may point to new and more effective ways of translating an understanding of innate im-munity into effective treatments for a leading cause of global morbidity and mortality. J. Leukoc. Biol