Approaching clinical reality: markers for monitoring systemic inflammation and sepsis

Abstract

The 'systemic inflammatory response syndrome (SIRS)' reflects a non-specific inflammatory reaction to various insults. In sepsis, defined as SIRS triggered by infection, a complex and overwhelming network of mediators contributes to the clinical syndrome. The host response in sepsis is characterized by unspecific physiologic criteria, which are unable to identify patients adequately who might benefit from either conventional anti-infective therapies or from novel therapies targeting specific mediators of sepsis. The early diagnosis of sepsis, the identification of the origin, adequate therapeutical management and the monitoring of the disease may help to overcome sepsis-associated mortality, which is unacceptably high and the third leading cause of death in Western Countries. Molecular techniques for identification of pathogens, their associated molecular patterns (PAMPs) and the ensuing host response may help to stratify patients with the urgent need for antibiotic therapy and those where it is safe to withhold or to de-escalate therapy. Beyond analysis of danger associated molecular patterns (DAMPs) at a single molecular level, the advent of genome-wide screening allows for an assessment of a wide variety of effectors and mediators in response to PAMPs. Also their purposeful targeting in animal models of sepsis revolutionized our understanding of pathophysiology in the critically ill. Molecular tools are about to challenge "state-of-the-art" diagnostic tests such as blood culture as they not only increase sensitivity but also dramatically reduce time requirements to identify pathogens and their resistance patterns. Mounting evidence suggests that our pathophysiological understanding might in the near future help to identify "patients at risk", i.e. those with a high likelihood to develop organ dysfunction and/or to guide therapeutic interventions in particular regarding resource-consuming and expensive therapies ("theragnostics"). The clinical utility for most of the discussed markers for monitoring systemic inflammation and sepsis has still to be evaluated in prospective trails. In conclusion, there is an unmet medical need for identification and validation of reliable biomarkers of sepsis; the clinical information obtained from the use of novel biomarkers might contribute to transform sepsis from a physiologic syndrome to a group of distinct biochemical disorders, to improve diagnosis and therapeutic decision making for high-risk patients, to monitor the response to therapy and to ensure the enrollment of seriously characterized patients in clinical studies.