Dysregulation of the immune response in severe sepsis.

Sepsis is systemic expression of a generalized activation of the host's innate immunity as a result of varied types of insults. This expression involves a cellular inflammatory response that has both proinflammatory and antiinflammatory components, the primary trigger for which is an intracellular oxidative stress, induced by receptor-mediated transmembrane signal transduction or direct noxious injury. Sepsis reflects the interaction between pro- and anti-inflammatory intracellular mechanisms, the uncontrolled activation of which leads to cell exhaustion, organ dysfunction, and death. Successful clinical trials of novel treatments for the management of severe sepsis share a common ability to down-regulate this overall response, restoring normal proinflammatory responsiveness and mitochondrial energetic function.