[Sepsis and organ failure--its pathogenesis and treatment]

Sepsis, septic shock, and multiple organ dysfunction are heterogeneous and sophisticated clinical syndromes which result from the interplay of mediators of cellular function and inflammation. Secondary mediators such as lipids (prostaglandin, thromboxane, platelet-activating factor), peptides (bradykinin, vasoactive intestinal peptide), amines (histamine, serotonin) and complements are key mediators which lead to the state of shock in human sepsis. Endotoxin may also cause multiple organ dysfunction syndrome (MODS). New antiendotoxin treatment and the strategy for sepsis including endotoxemia are reviewed. Monoclonal antibodies directed at core epitopes and lipid A (E5, HA1-A) could not reproduce the beneficial effects. Bactericidal/permeability increasing protein (BPI)). Endotoxin neutralizing protein (ENP)) and E5531 may have potential in the treatment of sepsis. Another treatment using extracorporeal endotoxin removal is reported. Polymyxin B immobilized fiber (PMX), commercialized as Toraymyxin, is now widely used in Japan for severe sepsis and septic MODS. PMX treatment improves the symptoms related to the septic state, a hemodynamic disorders, and cytokine levels including tumor mecrosis factor, interleukin (IL)-6, and IL-10, with a decrease in endotoxin levels. Phase II, III, and IV clinical trials with extracorporeal endotoxin removal by PMX revealed that endotoxin removal is helpful in the treatment of septic patients.