Long-chain n-3 fatty acids and inflammation: potential application in surgical and trauma patients

Lipids used in nutritional support of surgical or critically ill patients have been based on soybean oil, which is rich in the n-6 fatty acid linoleic acid (18:2n-6). Linoleic acid is the precursor of arachidonic acid (20:4n-6). In turn, arachidonic acid in cell membrane phospholipids is the substrate for the synthesis of a range of biologically active compounds (eicosanoids) including prostaglandins, thromboxanes, and leukotrienes. These compounds can act as mediators in their own right and can also act as regulators of other processes, such as platelet aggregation, blood clotting, smooth muscle contraction, leukocyte chemotaxis, inflammatory cytokine production, and immune function. There is a view that an excess of n-6 fatty acids should be avoided since this could contribute to a state where physiological processes become dysregulated. One alternative is the use of fish oil. The rationale of this latter approach is that fish oil contains long chain n-3 fatty acids, such as eicosapentaenoic acid. When fish oil is provided, eicosapentaenoic acid is incorporated into cell membrane phospholipids, partly at the expense of arachidonic acid. Thus, there is less arachidonic acid available for eicosanoid synthesis. Hence, fish oil decreases production of prostaglandins like PGE2 and of leukotrienes like LTB4. Thus, n-3 fatty acids can potentially reduce platelet aggregation, blood clotting, smooth muscle contraction, and leukocyte chemotaxis, and can modulate inflammatory cytokine production and immune function. These effects have been demonstrated in cell culture, animal feeding and healthy volunteer studies. Fish oil decreases the host metabolic response and improves survival to endotoxin in laboratory animals. Recently clinical studies performed in various patient groups have indicated benefit from this approach

The effects of fatty acids on lymphocyte functions

1. Lymphocytes play an important role in cell-mediated immunity and have been implicated in inflammatory and autoimmune diseases. 2. Unsaturated fatty acids, including oleic, linoleic, alpha-linolenic, arachidonic, eicosapentaenoic and docosahexaenoic acids, inhibit mitogen-stimulated lymphocyte proliferation in vitro. The inhibition of proliferation is dependent upon the concentration of fatty acid, the time during culture of fatty acid addition, the duration of exposure of the cells to the fatty acid and the chain length and degree of unsaturation of the fatty acid. 3. Unsaturated fatty acids suppress production of the immunoregulatory cytokine interleukin-2 by lymphocytes in vitro. 4. Triacylglycerols containing unsaturated fatty acids inhibit lymphocyte proliferation and natural killer cell activity in vitro. 5. Feeding weanling rats diets containing olive oil, evening primrose oil or fish oil results in suppression of lymphocyte proliferation. 6. Preliminary studies indicated that supplementation of the diet of healthy humans with fish oil-containing capsules suppresses lymphocyte proliferation and interleukin-2 production. 7. These effects, along with inhibitory effects upon the functions of other cells involved in the immune response, in particular monocytes and macrophages, indicate that certain unsaturated fatty acid-containing oils (particularly evening primrose oil and fish oil) may be of benefit in the treatment of inflammatory and autoimmune diseases