10 - Dietary fatty acids, lipid mediators, immunity, and inflammation

Abstract

The immune system provides a host defense against pathogens. Inflammation is part of normal host defense. However, uncontrolled, excessive, or unresolved inflammation is damaging to the host and can cause disease. Inflammatory diseases include rheumatoid arthritis (RA), inflammatory bowel diseases (IBDs), and asthma. Polyunsaturated fatty acids released from cell membrane phospholipids are substrates for the synthesis of eicosanoids and specialized pro-resolving mediators (SPMs) that are potent modulators of immunity and inflammation. In general, eicosanoids produced from arachidonic acid have proinflammatory actions, and some promote, while others suppress, the immune response. Eicosanoids produced from the omega-3 fatty acid eicosapentaenoic acid (EPA) are generally weak compared to those produced from arachidonic acid. The SPMs produced from EPA and docosahexaenoic acid (DHA) promote phagocytosis and are potent antiinflammatory and inflammation-resolving agents. Nonlipid mediator mechanisms of action also play a role in the effects of various fatty acids. At high doses, EPA+DHA has clinical benefits in RA, IBDs, and asthma. Provision of high-dose EPA+DHA in pregnancy appears to lower the risk of allergy and asthma in the offspring. Saturated and trans fatty acids promote inflammation, while EPA+DHA, and to a lesser extent α-linolenic acid, reduce inflammation, promote resolution of ongoing inflammation, and support immunity.