Protease inhibitors as a potential target in modulation of postischemic inflammation

Prevention of ischemia-reperfusion injury represents a main objective in infarction, cardiac surgery and organ transplantation. In the context of cellular homeostasis, postischemic inflammation may be understood in part as an initial physiological response to ischemia and reperfusion, aiming at restoration of tissue integrity. Polymorphonuclear cell infiltration and subsequent protease production, however, are crucial mechanisms contributing to tissue damage, cell necrosis and subsequent functional deficits. Therefore, inhibition of protease activity appears a promising target for modulating destructive processes of postischemic inflammation, while preserving its restorative nature. Recently, effects of secretory leukocyte protease inhibitor elafin and other protease inhibitors have been investigated in vivo and in vitro, which may provide a basis for future therapeutic strategies in postischemic inflammation.