Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale

The n-6 fatty acid arachidonic acid (AA; 20:4n-6) gives rise to eicosanoid mediators that have established roles in inflammation and AA metabolism is a long recognised target for commonly used anti-inflammatory therapies. It has generally been assumed that all AA-derived eicosanoids are pro-inflammatory. However this is an over-simplification since some actions of eicosanoids are anti-inflammatory (e.g. prostaglandin (PG) E-2 inhibits production of some inflammatory cytokines) and it has been discovered quite recently that PGE(2) inhibits production of inflammatory leukotrienes and induces production of inflammation resolving lipoxin A(4). The n-3 fatty acids from oily fish and fish oils, eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), are incorporated into inflammatory cell phospholipids in a time- and dose-dependent manner. They are incorporated partly at the expense of AA, but also of other n-6 fatty acids. EPA and DHA inhibit AA metabolism. Thus production of AA-derived eicosanoids is decreased by these n-3 fatty acids; this occurs in a dose-dependent manner. EPA gives rise to an alternative family of eicosanoids (e.g. PGE(3)) which frequently, but not always, have lower potency than those produced from AA. Recently a new family of EPA- and DHA-derived lipid mediators called resolvins (E- and D-series) has been described. These have potent anti-inflammatory and inflammation resolving properties in model systems. It seems likely that these mediators will explain many of the anti-inflammatory actions of n-3 fatty acids that have been described. In addition to modifying the profile of lipid-derived mediators, fatty acids can also influence peptide mediator (i.e, cytokine) production. To a certain extent this action may be due to the altered profile of regulatory eicosanoids, but it seems likely that eicosanoid-independent actions are a more important mechanism. Indeed effects on transcription factors that regulate inflammatory gene expression (e.g. nuclear factor kappa B) seem to be important. (c) 2009 Elsevier Masson SAS. All rights reserved.