Biologically active derivatives of fatty acids

Abstract

The causal role assigned to the E and F prostaglandins in inflammatory processes, implied by the antiinflammatory action of prostaglandin synthetase inhibitors, is not consistent with the findings reported here that a compound (MK-447) capable of increasing levels of these prostaglandins is antiinflammatory in classical animal models of acute inflammation. That both MK-447 and prostaglandin synthetase inhibitors depress the enzymatic formation of PGG₂ from arachidonic acid suggests that this endoperoxide plays a pivotal role in acute inflammation. However, in view of the intermediate nature of PGG₂, it seems likely that such a pivotal role for this substance is a function of its ability to be converted to other inflammatory mediators. Possible candidates for a causal role are thromboxane A₂ (TXA₂) prostacyclin (PGI₂), both of which derive from PGG₂. However, direct evidence is presented to show that an oxygen equivalent released in the enzymatic conversion of PGG₂ to PGH₂ is a prime factor in inflammation.