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 80241-A/asset/equation/feb2001457939080241a-math-si1.gif?v=1&s=c896d1721be9de8594d92c54c7b912a3f409cdac)
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].
