‘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 μM. Prostaglandin E₂, and leukotriene C₄ release by mouse macrophages stimulated with zymosan or ATP was not affected up to a concentration of 10 μm, nor was prostaglandin release by interleukin 1β-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 μg/paw) or systemic administration (1 or 4 s.c.). These results do not support the claim of potent phospholipase A₂-inhibitory and anti-imflammatory activity of the ‘antiflammins’ P1 and P2 [1].