Disorder of systemic inflammation in sepsis and trauma: A systems perspective

The inflammatory response is highly integrated and involves regulatory elements released from the cells of the immune system, humoral factors, the endothelium, and endogenous danger signals. Once activated, the goals of the inflammatory response are to activate the cellular immune response in order to ward off penetrating pathogens and to initiate tissue repair mechanisms. The magnitude of the systemic response is proportional to the severity of the initial insult on the background of the genetic milieu of the individual. The inflammatory response is closely regulated, and a counter-anti-inflammatory response keeps it in check. When excessive or sustained, this immunoinflammatory response gives way to prolonged immunosuppression, leaving the individual susceptible to nosocomial infections and prolonged intensive care unit (ICU) stay. Only by understanding how the immunoinflammatory response becomes disordered can we devise strategies to limit the deleterious consequences.