The Effect of Dietary Supplementation with n—3 Polyunsaturated Fatty Acids on the Synthesis of Interleukin-1 and Tumor Necrosis Factor by Mononuclear Cells

Stefan Endres, Reza Ghorbani, Vicki E. Kelley, Kostis Georgilis, Gerhard Lonnemann, Jos W.M. Van Der Meer, Joseph G. Cannon, Tina S. Rogers, Mark S. Klempner, Peter C. Weber, Ernst J. Schaefer, Sheldon M. Wolff, Charles A. Dinarello

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Abstract

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. INTERLEUKIN-1 and tumor necrosis factor are polypeptide cytokines synthesized by monocytes and other cells in response to injury, as well as to infectious, inflammatory, or immunologic challenges.1 2 3 These cytokines induce local inflammatory changes and mediate several systemic acute-phase responses.4,5 Moreover, interleukin-1 and tumor necrosis factor often act synergistically — e.g., on vascular endothelium,6 insulin production,7 and the synthesis of metabolites of arachidonic acid.8 The n—3 (also called omega—3) fatty acids are polyunsaturated fatty acids in which the last double bond is located between the third and fourth carbon atom from the methyl end of the fatty acid chain. These fatty…

Original languageEnglish (US)
Pages (from-to)265-271
Number of pages7
JournalNew England Journal of Medicine
Volume320
Issue number5
DOIs
StatePublished - Feb 2 1989

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Endres, S., Ghorbani, R., Kelley, V. E., Georgilis, K., Lonnemann, G., Van Der Meer, J. W. M., Cannon, J. G., Rogers, T. S., Klempner, M. S., Weber, P. C., Schaefer, E. J., Wolff, S. M., & Dinarello, C. A. (1989). The Effect of Dietary Supplementation with n—3 Polyunsaturated Fatty Acids on the Synthesis of Interleukin-1 and Tumor Necrosis Factor by Mononuclear Cells. New England Journal of Medicine, 320(5), 265-271. https://doi.org/10.1056/NEJM198902023200501