N-3 POLY-UNSATURATED FATTY-ACIDS, INTERLEUKIN-1, AND TUMOR NECROSIS FACTOR

We examined whether the synthesis of interleukin-1 or tumor necrosis factor, two cytokines with potent inflammatory activities, is influenced by dietary supplementation with n—3 fatty acids.Nine healthy volunteers added 18 g of fish-oil concentrate per day to their normal Western diet for six weeks. We used a radioimmunoassay to measure interleukin-1 (IL-1β and IL-1α) and tumor necrosis factor produced in vitro by stimulated peripheral-blood mononuclear cells. With endotoxin as a stimulus, the synthesis of IL-1β was suppressed from 7.4±0.9 ng per milliliter at base line to 4.2±0.5 ng per milliliter after six weeks of supplementation (43 percent decrease; P = 0.048). Ten weeks after the end of n-3 supplementation, we observed a further decrease to 2.9±0.5 ng per milliliter (61 percent decrease; P = 0.005). The production of IL-1α and tumor necrosis factor responded in a similar manner. Twenty weeks after the end of supplementation, the production of IL-1βIL-1α, and tumor necrosis factor had returned to the presupplement level. The decreased production of interleukin-1 and tumor necrosis factor was accompanied by a decreased ratio of arachidonic acid to eicosapentaenoic acid in the membrane phospholipids of mononuclear cells.We conclude that the synthesis of IL-1β, IL-1α, and tumor necrosis factor can be suppressed by dietary supplementation with long-chain n—3 fatty acids. The reported antiinflammatory effect of these n—3 fatty acids may be mediated in part by their inhibitory effect on the production of interleukin-1 and tumor necrosis factor