Role of prostaglandin endoperoxide PGG₂ in inflammatory processes

Abstract

SINCE the discovery that non-steroidal anti-inflammatory agents (NSAI) are potent inhibitors of prostaglandin synthetase^1–3, there has been controversy about the role of primary prostaglandins (PGEs+PGFs=PGs) in inflammatory diseases. A parallel has been demonstrated between the ability of drugs such as indomethacin and aspirin to inhibit cyclo-oxygenase, the initial step leading to the formation of PGs, and anti-inflammatory activity^4–6. The failure of administered PGs to fully mimic inflammation processes, however, is not consistent with this concept^7,8, and further studies have shown that other products derived from the reaction of cyclo-oxygenase with arachidonic acid (PGG₂, PGH₂ and thromboxane A₂) although quite labile, have biological activities exceeding the potency of the PGs themselves^9,10. Since these ephemeral mediators are also subject to regulation by NSAI they too must be considered as potential causal agents of inflammation. We have investigated this possibility by examining the action of several NSAI on the total pattern of arachidonic acid oxygenation products. The results indicate that the endoperoxide PGG₂ has a pivotal role in acute inflammation.