Pathogenesis of sepsis: current concepts and emerging therapies

The treatment of sepsis and septic shock is an important clinical problem. While effective antibiotic intervention and strong supportive care have improved survival, mortality remains at unacceptable levels. The induction of systemic inflammation appears to be clearly mediated through a variety of microbial products, not all of which have uniform ability to induce gene expression in host inflammatory mediator cells. The available evidence would support the conclusion that microbial mediators can function synergistically in the induction of host inflammation, providing a potential explanation that anti-endotoxin and anti-inflammatory agents have not been particularly successful in clinical trials to treat septic shock. The identification of specific recognition molecules on the surface of inflammatory mediator cells responsible for initiation of signal transduction, as well as the elucidation of the specific molecular pathways leading to gene expression, provide new opportunities for the development of effective intervention strategies for treatment of septic shock.