In vitro and in vivo effects of the anti-inflammatory peptides, antiflammins.

The anti-inflammatory synthetic polypeptides referred to as antiflammins are thought to be inhibitors of phospholipase A2 (PLA2) (EC 3.1.1.4). These peptides are from the sequence of amino acids of greatest similarity between uteroglobin and lipocortin I. The effect of these peptides was studied on PLA2 activation in rat platelets and on acute inflammatory models after local or parenteral administration of drug. We found that antiflammins decreased collagen-induced platelet activation, but had no effect when arachidonic acid was used as activator. The peptides were able to inhibit acute inflammatory processes induced by carrageenan or phorbol esters when administered locally or parenterally. However, antiflammins had no effect on inflammation induced by exogenous PLA2 administration. These results indicate that the antiflammins may have a direct inhibitory effect on PLA2 activation but not on the enzyme or enzyme-substrate interaction.