'Antiflammins': Two Nonapeptide Fragments of Uteroglobin and Lipocortin I Have No Phospholipase A2-inhibitory and Anti-inflammatory Activity

The 'antiflammin' nonapeptides P1 and P2 [(1988) Nature 335, 726-730] were synthesized and tested for inhibition of phospholipase A2 and release of prostaglandin E2 and leukotriene C4 in stimulated cells in vitro, and in vivo for anti-inflammatory activity in rats with carrageenan-induced paw oedema. Porcine pancreatic phospholipase A2 was not inhibited at concentrations of 0.5-50 microM. Prostaglandin E2 and leukotriene C4 release by mouse macrophages stimulated with zymosan or ATP was not affected up to a concentration of 10 microM, nor was prostaglandin release by interleukin 1 beta-stimulated mesangial cells and angiotensin II-stimulated smooth muscle cells. Both peptides exhibited no anti-inflammatory activity in carrageenan-induced rat paw oedema after topical (250 micrograms/paw) or systemic administration (1 or 4 mg/kg s.c.). These results do not support the claim of potent phospholipase A2-inhibitory and anti-inflammatory activity of the 'antiflammins' P1 and P2.