The first MMP in sepsis

Systemic inflammatory response syndrome (SIRS) is the number one killer in intensive care units. It is a collective name referring to an exaggerated inflammatory response that can have several etiologies and can be observed, for example, after poly trauma, burns or in post‐operative patients. The most reputed condition of SIRS, however, is sepsis, which is the result of a—usually microbial infection. Sepsis associated with organ failure is called severe sepsis, and sepsis associated with persistent blood pressure loss, despite fluid resuscitation, is called septic shock. In the USA, some 900,000 new cases of sepsis are counted yearly, which increases by 1.5% per year. In Europe, about 27% of sepsis, 32% of severe sepsis and 54% of septic shock patients will not survive their admission. Despite decades of intensive research, the list of new therapeutics for the treatment of sepsis is very short. Hence, sepsis has been called ‘the graveyard for pharmaceutical companies’ (Riedemann et al, 2003).But what makes sepsis such a difficult condition to deal with? First, it is usually an acute condition and patients arriving at the ICU are already infected. Second, many infectious agents have developed antibiotic resistances. Third, the response of patients is very complex and differs significantly depending on the infectious agent, but also depending on patient‐specific aspects, such as age, gender and genetic background. Moreover, the host response seems to develop from an initially hyper‐inflammatory phase to a hypo‐inflammatory phase. Infectious agents activate the innate immune system and inflammation through several mechanisms. The inflammatory condition of the host has been considered as dangerous and many clinical trials using …