The role of prostaglandins in inflammation.

Abstract

The possible involvement of prostaglandins (PGs) in the inflammatory response has received a great deal of attention since the nonsteroidal anti-inflammatory drugs (NSAID) were found to inhibit PG synthesis (Vane, 1911; Smith and Willis, 1971; Ferreira et al., 1971). Almost all mammalian cells have the ability to synthesize PGs. In fact, the precursors of the PGs are polyunsaturated fatty acids in cell membranes, derived from the dietary essential fatty acids (EFAs). These fatty acids are mainly found in the phospholipids imparting important structural properties to the cell. In 1929, Burr and Burr studied the pathologic syndrome that appeared when rats were kept on a fat-free diet. Later, it was appreciated that linoleic acid caused the deficiency state. Fulco and Mead (1959) demonstrated in EFA deficient animals, that oleic acid substitutes for linoleic acid with the resultant production of eicosatrienoic acid, which can substitute for arachidonate in cell membranes, but apparently cannot prevent the deficiency. After von Euler in 1935 had studied the polar fatty acids extracted from seminal plasma and termed them prostaglandins, van Dorp (1964) and Bergström et al. (1964) simultaneously introduced the concept that PGs were derived from the 20-carbon essential fatty acids (Fig. 1). It is now generally accepted that the conversion of arachidonic acid to PGs accounts for some of the pathology when animals are restricted in their dietary fat.