DIFFERENTIAL-EFFECTS OF OMEGA-6 AND OMEGA-3-FATTY-ACIDS ON INTERLEUKIN-2 PRODUCTION AND MESSENGER-RNA EXPRESSION BY EL-4.IL-2 CELLS

Our studies with lupus-prone (NZBxNZW)F-1 (B/W) female mice have indic ated that dietary omega-3 lipids (menhaden oil) significantly extend t he life span and delay the onset of autoimmune disease, while omega-6 lipids (corn oil) shorten the life span by accelerating the onset and progression of autoimmune disease, probably by altering the cell and s ubcellular membrane fatty acid composition. To understand the mechanis ms through which omega-6 (linoleic acid, 18:2, and arachidonic acid, 2 0:4) and omega-3 (eicosapentanoic acid, 20:5, and docosahexanoic acid, 22:6) lipids exert their differential effects, we have studied the ef fects of these fatty acids in vitro on cell proliferation, peroxidatio n, interleukin-2 (IL-2) production, IL-2 mRNA levels, and surface IL-2 receptor (IL-2R) expression in an IL-2 producing mouse lymphoma cell line (EL-4.IL-2;EL-4). When EL-4 cells were cultured in the presence o f individual omega-6 and omega-3 fatty acids (at a final concentration of 10 mu g/mL), the respective fatty acid was found to incorporate in to the cells at a significant level, and no adverse effects were noted either on the viability of the cells or on the de novo DNA synthesis. In addition, lipid peroxidation, as measured by the generation of thi obarbituric acid-reactive substances, was significantly higher (P < 0. 05) in cells incubated with 20:4 omega-6 as compared with control cell s (to which no fatty acid was added). Also, 20:4 omega-6 significantly inhibited (P < 0.05) IL-2 production when compared with other fatty a cids. Northern blot analysis revealed that this inhibition in IL-2 pro duction by 20:4 omega-6 was at the gene level, as seen by an inhibitio n in phorbol-12-myristate-13-acetate induced IL-2 mRNA levels by 20:4 omega-6. Compared with saturated fatty acids, both omega-6 and omega-3 lipids induced higher IL-2R surface expression, as seen by flow cytom etry. These studies suggest that dietary omega-3 lipids lower membrane lipid peroxidation, and thereby may preserve normal immunological fun ctions that may delay the course of autoimmune disease in B/W mice.