Santoli D, Zurier R B
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
J Immunol. 1989 Aug 15;143(4):1303-9.
Essential fatty acids, from which PG derive, can participate in development and regulation of immune responses and have been shown to suppress inflammation and tissue injury in animal models. In this report, we investigate the effects of the immediate (DGLA, precursor to PGE1), arachidonic acid (AA, PGE precursors, dihomogamma linolenic acid (DGLA, precursor to PGE1), arachidonic acid (AA, precursor to PGE2), and eicosapentaenoic acid (EPA, precursor to PGE3) on IL-2 production by PHA-stimulated human PBMC. DGLA and AA inhibited IL-2 production in a dose-dependent manner: half-maximal inhibition was obtained by using the fatty acids at the dose of 10 micrograms/ml without significant effects on cell viability. EPA inhibited IL-2 production by PBMC of only some donors. Incubation of cells in the presence of oleic, stearic, and palmitic acids, which are not PG precursors, did not affect mitogen-induced IL-2 production. A progressive increase in incorporation of DGLA into cellular lipids was observed over a 48-h incubation period. IL-2 production was reduced also when PBMC were pretreated overnight with DGLA or AA and washed before exposure to PHA. Whereas addition of the cyclo-oxygenase inhibitor, indomethacin, at the time of mitogenic stimulation led to increased IL-2 production and prevented mitogen- and fatty acid-induced increases in PGE release, it had no significant effect on the capacity of the fatty acids to suppress IL-2 production. Time course experiments showed that DGLA and AA inhibited IL-2 production even at times of minimal or no PGE release by the treated cultures. Moreover, DGLA and AA inhibited IL-2 production by the human leukemia T cell line Jurkat which, when appropriately induced, is able to release high levels of IL-2 in the absence of accessory cells and measurable PGE production. Taken together, these data indicate that essential fatty acids inhibit IL-2 production directly without conversion into their cyclo-oxygenase pathway products, and suggest that human lymphocyte function may be altered profoundly by small changes in their fatty acid profile.
前列腺素（PG）的前体——必需脂肪酸，可参与免疫反应的发育和调节，并已在动物模型中显示出能抑制炎症和组织损伤。在本报告中，我们研究了直接作用的脂肪酸（二高γ-亚麻酸，PGE1的前体）、花生四烯酸（AA，PGE的前体）、二高γ-亚麻酸（DGLA，PGE1的前体）、花生四烯酸（AA，PGE2的前体）和二十碳五烯酸（EPA，PGE3的前体）对PHA刺激的人外周血单个核细胞（PBMC）产生IL-2的影响。DGLA和AA以剂量依赖的方式抑制IL-2的产生：在脂肪酸浓度为10微克/毫升时可获得半数最大抑制，且对细胞活力无显著影响。EPA仅抑制部分供体的PBMC产生IL-2。在油酸、硬脂酸和棕榈酸（它们不是PG的前体）存在的情况下培养细胞，不影响有丝分裂原诱导的IL-2产生。在48小时的孵育期内，观察到DGLA掺入细胞脂质的量逐渐增加。当PBMC用DGLA或AA预处理过夜并在暴露于PHA之前洗涤时，IL-2的产生也会减少。虽然在有丝分裂原刺激时加入环氧化酶抑制剂吲哚美辛会导致IL-2产生增加，并阻止有丝分裂原和脂肪酸诱导的PGE释放增加，但它对脂肪酸抑制IL-2产生的能力没有显著影响。时间进程实验表明，即使在处理的培养物中PGE释放极少或没有释放时，DGLA和AA也能抑制IL-2的产生。此外，DGLA和AA抑制人白血病T细胞系Jurkat产生IL-2，该细胞系在适当诱导时，能够在没有辅助细胞和可测量的PGE产生的情况下释放高水平的IL-2。综上所述，这些数据表明必需脂肪酸直接抑制IL-2的产生，而无需转化为其环氧化酶途径产物，并表明人类淋巴细胞功能可能因其脂肪酸谱的微小变化而发生深刻改变。
