Implications for eicosapentaenoic acid- and docosahexaenoic acid-derived resolvins as therapeutics for arthritis.

Omega-3 polyunsaturated fatty acids are essential for health and are known to possess anti-inflammatory properties, improving cardiovascular health as well as benefiting inflammatory diseases. Indeed, dietary supplementation with omega-3 polyunsaturated fatty acids has proved efficacious in reducing joint pain, morning stiffness and nonsteroidal anti-inflammatory drugs usage in rheumatoid arthritis patients. However, the mechanisms by which omega-3 polyunsaturated fatty acids exert their beneficial effects have not been fully explored. Seminal discoveries by Serhan and colleagues have unveiled a novel class of bioactive lipid mediators that are enzymatically biosynthesized in vivo from omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), termed resolvins, protectins and maresins. These bioactive pro-resolving lipid mediators provide further rationale for the beneficial effects of fish-oil enriched diets. These endogenous lipid mediators are spatiotemporally biosynthesized to actively regulate resolution by acting on specific G protein-coupled receptors (GPCRs) to initiate anti-inflammatory and pro-resolving signals that terminate inflammation. In this review, we will discuss the mechanism of actions of these molecules, including their analgesic and bone-sparing properties making them ideal therapeutic agonists for the treatment of inflammatory diseases such as rheumatoid arthritis.