Sepsis

Sepsis is a complex immune disorder that results in 750,000 hospitalizations annually in the United States alone. In addition to posing an immense health hazard with a mortality rate of 20-50%, it is also a huge economic healthcare burden with the patients consuming half of the ICU resources in the country. In October 2011, the only FDA approved drug for the treatment of sepsis (Xigris) was withdrawn from market following the much anticipated results of the clinical trial (PROWESS-SHOCK) where it failed to show any survival benefit for severe sepsis and septic shock patients. As a result we are now left with no effective preventive or treatment options for this deadly immune disorder, despite three decades of active research. Why has it been so hard to tackle sepsis? One obvious reason is the complexity of this disorder as it is thought to be interplay of multiple host immune pathways. The second likely reason is that most of the research has been focused on initiation of inflammatory response when the need is to take into account factors responsible for exaggeration of ongoing inflammation as well as lack of negative regulatory mechanisms/resolution of inflammation/restoration of homeostasis