THE ROLE OF PHAGOCYTE PROTEINASES AND PROTEINASE-INHIBITORS IN MULTIPLE ORGAN FAILURE

Although numerous other inflammatory mediators are important, the foll owing review of our research and that of other authors reveals a promi nent role for the phagocyte proteinases, polymorphonuclear (PMN) elast ase and cathepsin B, in the development of multiple organ failure. The release of these enzymes in relation to the severity of trauma- and/o r infection-induced inflammation was clearly verified in a variety of clinical studies. The amounts of the extracellular(y discharged phagoc yte proteinases were highly predictive of forthcoming organ failure an d ultimate patient outcome. Moreover, the consumption of important pro teinase inhibitors (e.g., alpha(1)-proteinase inhibitor, antithrombin III) and other plasma proteins (e.g., fibrinogen), which are highly su sceptible to proteolytic degradation, coincided with the occurrence of proteolytic activity, especially that of PMN elastase. Therefore, the therapeutic use of specific PMN elastase and/or thrombin inhibitors s hould prevent multiple organ failure or at least reduce severe signs o f inflammation.