n-6 and n-3 essential fatty acids in rheumatoid arthritis and other rheumatic conditions.

The essential fatty acids (EFA) have unique roles as precursor molecules of chemical regulators of inflammatory and immune cell function (Belch, 1989). These are the leukotrienes (LT) and the prostaglandins (PG). These compounds are synthesized and released by almost every tissue in the body, and participate in many biological functions, including the inflammatory and immune processes. Most work has focused on arachidonic acid, the precursor of the 2-series PG and the 4-series LT. Altering the EFA content in the diet or administering different EFA as supplements can modify the production of the various PG and LT by altering the substrate EFA. For example, the ingestion of a diet rich in borage (Borago ogicinalis) oil (Starflower Oil) or evening primrose (Oenothera biennis) oil (EPO) will elevate levels of dihomo-y-linolenic acid, which will result in an increase in the 1-series PG, e.g. PGEl (Manku et al. 1986). In common with all PG, PGEl is able to induce the cardinal signs of inflammation, i.e. redness, oedema, pain, heat and loss of function. In contrast, however, the action of PGEl on the inflammatory cells, the polymorphonuclear leucocytes, is mostly inhibitory (Weissmann et al. 1980). PGEl increases intracellular cAMP and it is this increase in polymorphonuclear cell cAMP which decreases the release of lysosomal enzymes, decreases polymorphonuclear cell chemotaxis and the margination and adherence of leucocytes in the blood vessels. Similarly, the effect of PGEl on the lymphocyte is thought to be inhibitory (Rogers, 1985). Exogenous addition of PGEl inhibits both in vitro function of lymphocytes and in vivo responses mediated by lymphocytes. It has been suggested that PGEl has a negative feedback role in chronic inflammation, initially aiding development of the cardinal signs of inflammation followed by a later suppressant effect, and this anti-inflammatory effect might be useful in a disease characterized by inflammation, such as rheumatoid arthritis (RA; Fig. 1). A further benefit of a diet rich in compounds containing y-linolenic acid (GLA; which will be metabolized to dihomo-y-linolenic acid) is the inhibitory effect on LT synthesis. Dihomo-y-linolenic acid cannot itself be converted to LT, but can form a 15-hydroxyl derivative that blocks transformation of arachidonic acid to LT (Voorlees, 1983). Additionally, there may be formation of a 13-hydroxyoctadecadienoic acid product which may also have anti-inflammatory effects. Thus, increasing GLA intake will allow its metabolism to dihomo-y-linolenic acid, when it will act as a competitive inhibitor of the 2-series PG and 4-series LT and thus potentially suppress inflammation (Jantti et al. 1989; Oxholm e? al. 1992). In the same way it is postulated that eicosapentaenoic acid (EPA) is metabolized to the less-potent (in terms of inflammation) PG of the 3-series and 5-series LT (Prescott e? al. 1985). Fish oil contains EPA and docosahexaenoic acid, both of which have been shown to modulate immune function. Studies of normal volunteers ingesting high concentrations of EPA confirm a shift of neutrophil production away from LTB4 towards LTB5 (Prescott et al. 1985). EPA also inhibits the polymorphonuclear cell chemotaxis.