The basic science of sepsis

The understanding of the basic science of sepsis has increased considerably in recent years but such advances have not had a significant impact upon the development of new therapeutic strategies. Patients with severe sepsis die from multiple organ failure but it is not known how an infection that is normally combated in the majority of individuals produces such catastrophic events in these patients. Although the consensus of opinion is that the pathology of sepsis is multifactorial, an inappropriate activation of the immune system seems to be a key stage in the initiation of organ insult. From animal experiments there is compelling evidence that cytokines such as TNFα and IL-1 occupy a pivotal role in organ failure but in randomized control trials antagonists of these molecules have not improved survival in patients with severe sepsis. We propose that it may be more beneficial to target subsets of neutrophils that have the potential to induce organ failure either directly or indirectly through disruptions of the microvasculature.