ABSTRACT
Beside the therapeutic animal experiments, preliminary clinical studies have proven the postulated positive effects of thrombin inhibition on the hemostatic system by antithrombin (AT) III supplementation in severely ill patients. Proteolysis-induced pathomechanisms seem to play a major role in the primary response to and the ultimate outcome of the organism to inflammatory stimuli such as tissue destruction due to multiple trauma and major surgery or invasive microbes and endotoxins in sepsis. The inflammatory effector role proved especially true for polymorphonuclear (PMN) elastase, because the destructive potency of this proteinase could be convincingly demonstrated at least on vital humoral proteins in relation to the propagation of organ dysfunctions in traumatized as well as septic patients. In addition to the proof of PMN elastase release in septic/endotoxic situations, pigs are the only animal species in which an extracellular discharge of the monocyte/macrophage-derived cysteine proteinase cathepsin B above normal has been reliably demonstrated after endotoxin infusion so far.
