CYTOKINE PRODUCTION AND DNA-SYNTHESIS BY HUMAN PERIPHERAL LYMPHOCYTESIN RESPONSE TO PALMITIC, STEARIC, OLEIC, AND LINOLEIC-ACID

Effects of palmitic, stearic, oleic, and linoleic acid on mitogen-indu ced DNA synthesis, on production of IL-1 beta, IL-2, IFN-gamma, and TN F-alpha, and on IL-2R expression were determined in human peripheral l ymphocytes. Free fatty acids (FFA) were added over a wide range of con centrations to cells cultured under serum free conditions with fatty a cid free albumin. DNA synthesis was stimulated by low and inhibited by high FFA concentrations. Physiological concentrations were stimulator y, except for linoleic acid. Cytokine production became affected by al l FFA tested. Palmitic acid enhanced the release of IFN-gamma at conce ntrations that diminished TNF-alpha production. Saturated fatty acids were significantly more potent than unsaturated fatty acids in affecti ng cytokine production. IFN-gamma secretion was significantly more sti mulated or inhibited by the various FFA, compared with the other cytok ines. IL-2R expression correlated with the production of IL-2. When te sted in combination, stimulatory as well as inhibitory effects of the individual FFA became attenuated. It is suggested that palmitic, stear ic, oleic, and linoleic acid are physiological regulators of DNA synth esis and cytokine release in human peripheral lymphocytes. Modulation of FFA ratios may be an effective means for the fine tuning of the imm une system. As secretory mechanisms of cytokines appear to exhibit sub strate specificity for FFA, the release of individual cytokines may be selectively influenced by FFA. (C) 1994 Wiley-Liss, Inc.