Effects of an anti-inflammatory peptide (antiflammin 2) on cell influx, eicosanoid biosynthesis and oedema formation by arachidonic acid and tetradecanoyl phorbol dermal application.

Antiflammins are synthetic peptides with sequence homology to proteins inhibitory for phospholipase A2 (EC 3.1.1.4). The effect of antiflammin 2 on murine arachidonate or 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear oedema has been studied. Topical application of arachidonic acid (AA) produced a short-lived oedema response with rapid onset associated with marked increases in prostaglandin E2 levels. TPA produced a longer-lasting oedema associated with marked influx of neutrophils and mononuclear cells as well as predominant formation of leukotriene B4 (LTB4). Topical pretreatment with indomethacin or dexamethasone reduced plasma leakage, oedema and prostaglandin E2 biosynthesis in AA-induced oedema, whereas antiflammin 2 had no effect. However, topical pretreatment with antiflammin 2 dose-dependently reduced plasma leakage, cell influx, oedema and LTB4 levels in response to TPA. These results indicate that the anti-inflammatory effect of antiflammins can be attributed to AA mobilization and/or 5 lipoxygenase inhibition but can be dissociated from an effect on arachidonic acid metabolism by the cyclooxygenase pathway.