SEPSIS SIRS - PATHOMECHANISMS AND NEW THE RAPEUTIC PERSPECTIVES/

In spite of aggressive antibiotics and cardiovascular and pulmonary su pport the mortality from sepsis remains high at 30%-70%. The lack of e ffective treatment reflects the complex pathogenesis of sepsis and sys temic inflammatory response syndrome (SIRS), Recent discoveries have c larified a number of key steps in the sequence of events, Infectious a s well as non-infectious Insults are capable of stimulating the host i mmune system to elaborate a number of important mediators such as cyto kines, eicosanoids, complement and coagulation components, kinine, pla telet-activating factor, nitric oxide, oxygen radicals and other media tors that can produce profound effects on vascular tone and permeabili ty. If this cascade is not interrupted, it will result in cardiovascul ar and pulmonary Insufficiency and finally in multiple organ system fa ilure. Based on proposed pathomechanisms of SIRS se-lected new therapi es designed to inhibit bacterial toxins or endogenous mediators of inf lammation have been developed. Experimental and clinical data using a variety of specific inhibitors and receptor antagonists are reviewed. The presently controversial results require further trials and an impr oved scientific understanding of the complex inflammatory reaction to reduce the high mortality associated with SIRS.