Sepsis Strategies in Development

Severe sepsis, defined as inflammation and organ failure due to infection, continues to result in a mortality of approximately 30% despite advances in critical care. Current therapy includes timely administration of antibiotics, source control of infection, aggressive fluid resuscitation, support of failing organs, and use of activated protein C where clinically indicated. Bacterial mediators, including endotoxin and superantigens, as well endogenous proinflammatory cytokines are considered important to the pathogenesis of sepsis-induced organ failure and are being targeted with numerous molecules and removal devices. Additional therapeutic strategies are aimed at restoring the natural anticoagulant levels, blocking deleterious effects of the complement cascade, reversing cytopathic hypoxia, and inhibiting excessive lymphocyte apoptosis. Molecules with pluripotent activity, such as interalpha inhibitor proteins and estrogen-receptor ligands, are also being investigated.