Markers of organ damage

Among a plethora of markers of sepsis, multiple organ dysfunction failure syndrome (MOFS) or systemic inflammatory response syndrome (SIRS), blood levels of lipopolysaccharide (LPS) are not necessarily indicative of the severity oforgan damage. The focusing on the LPS transduction system, e.g., expression. of LPS-binding protein (LBP), ceramide and CD 14 (especially sCD 14) molecules or translocation of NF-kB molecules is more promising. Among cytokines, a special position occupy TNF-alpha (fast response) and IL-1beta (a more delayed response). Apart from the role of cytokines as markers, they also pretend to be of therapeutic value, e. g., soluble TNF receptors (sTNFR), monoclonal IL-1 antibodies (mAb) IL-1 receptor antagonists (IL-1ra), inhibitors of IL-1beta converting enzyme (ICE inhibitors). Another field of therapeutic exercises includes lipid markers and nitric oxide (NO). Inhibitors of cyclooxygenases (COX) with a prevalence towards COX-2 (e.g., ibuprofen, melloxicam) or thromboxane synthase inhibitors (e.g., camonagrel) are likely to hinder the formation of cytotoxic thromboxanes and isoprostanes. Prostacyclin analogues (e.g., iloprost) and prostaglandin E1 (PGE(1)) can offer cytoprotection, increase tissue blood flow and activate fibrinolysis. Like these prostanoids, PAF antagonists (e.g., BN 52021 or TCV-309) may inhibit LPS-induced generation of cytokines. Inhibitors of NO synthase (NOS inhibitors, e.g., L-NMMA or L-NAME) were tried in septic patients. On the other hand inhalations of NO (10-40 ppm) were also given and antioxidant therapy was used. The multiplicity of therapeutic approaches indicates that none of these treatments is satisfactory. Moreover, it is doubtful if markers of MOFS are the proper targets for therapeutic intervention. Perhaps the markers only indicate the number of inflammatory cells which have been recoded to apoptosis, and nothing can be done to prevent their programmed death.