Enzymes and Antienzymes in Inflammatory Reactions

¹ Institute of Pharmacology, Faculty of Medicine, University of Pisa, Pisa, Italy

The role of enzymatic activation in inflammatory processes can have a double aspect, that of aiding and provoking inflammation and that of inhibiting and blocking it. This phenomenon is evident particularly with regard to proteases, which can cause inflammation or the formation of antiproteases that are able to cause their blockage and thus indirectly have an anti-inflammatory effect.

We demonstrated that many drugs that inhibit proteases also have an anti-inflammatory effect. The protease inhibition can occur directly on free enzymes or prevent the liberation of enzymes from their sites of production. At the cellular level, the enzymatic equilibrium between cyclic AMP and phosphodiesterase, which is analogous to that which occurs at the level of proteases, can be altered by the presence of anti-inflammatory drugs. We demonstrated how the increased concentration of cyclic AMP can have an inhibitive effect on some inflammatory and immunologic phenomena. We showed that experimental edema of the rat paw can be elicited by cyclic AMP administration and that phosphodiesterase inhibitors can increase the effect. The vessel permeability activity of PGE₁ can be blocked by antiprotease administration.