Therapeutic approaches to innate immunity: Severe sepsis and septic shock

Severe sepsis leading to shock is the principal cause of death in non-cardiac intensive care units. This condition develops because of a dysregulation in host responses, such that the mechanisms initially recruited to fight infection produce life-threatening tissue damage and death. Recent advances in our understanding of innate immunity, and the interaction between the inflammatory and the haemostatic cascades, are affording new opportunities for therapeutic development. This article discusses selected pathophysiological mechanisms that might yield to therapeutic intervention, considers rationales for the resurrection of previously failed drugs, and highlights new targets that have shown promise in preclinical studies.