Lefkowith J B, Morrison A, Lee V, Rogers M
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
J Immunol. 1990 Sep 1;145(5):1523-9.
Dietary polyunsaturated fatty acid modulation has been used as an anti-inflammatory strategy in experimental models of disease as well as in clinical trials. To elucidate the mechanisms underlying the anti-inflammatory effects of manipulating dietary polyunsaturated fatty acids, the in vivo effects of essential fatty acid (EFA) deficiency and (n-3) fatty acid supplementation were contrasted using a model of acute inflammation induced by the i.p. injection of zymosan into mice. Both diets led to a substantial decrease in tissue (n-6) fatty acid content. EFA deficiency was also characterized by the accumulation of (n-9) fatty acids, particularly 20:3 (n-9), the fatty acid that uniquely characterizes the deficiency state. Dietary (n-3) fatty acid supplementation led instead to marked increases in (n-3) fatty acids, especially 20:5 (n-3). With respect to the antiinflammatory effects of the two diets, EFA deficiency, but not (n-3) fatty acid supplementation, depleted levels of resident peritoneal macrophages. EFA deficiency was also more effective than (n-3) fatty acid supplementation in inhibiting the influx of polymorphonuclear neutrophils in response to zymosan. The effect of the two diets on the in vivo generation of leukotriene(LT)B also differed markedly. EFA deficiency completely inhibited the synthesis of LTB. Dietary (n-3) fatty acid supplementation, in contrast, reduced the production of LTB4 by only 50%. With (n-3) fatty acid supplementation LTB5 was produced. The more modest effect of (n-3) fatty acid supplementation in decreasing LTB4 generation was not due to blockade of the cyclooxygenase pathway. EFA deficiency, but not (n-3) fatty acid supplementation, was associated with the decreased synthesis of thromboxane. Although dietary fatty acid modulation has been shown to diminish platelet activating factor (PAF) synthesis, studies using the PAF receptor blocker, L659989, established that PAF was not a significant factor in the elicitation of leukocytes in this model of inflammation. In summary, the anti-inflammatory effect of EFA deficiency was more marked that that of dietary (n-3) fatty acid supplementation in acute inflammation. This difference in anti-inflammatory potential appeared to be due to either the greater effect of EFA deficiency in decreasing levels of resident peritoneal macrophages or in suppressing the in vivo generation of LTB4.
在疾病的实验模型以及临床试验中，膳食多不饱和脂肪酸调节已被用作一种抗炎策略。为了阐明调控膳食多不饱和脂肪酸抗炎作用的潜在机制，利用腹腔注射酵母聚糖诱导小鼠急性炎症的模型，对比了必需脂肪酸（EFA）缺乏和（n-3）脂肪酸补充的体内效应。两种饮食均导致组织中（n-6）脂肪酸含量大幅下降。EFA缺乏还表现为（n-9）脂肪酸的积累，尤其是20:3（n-9），这种脂肪酸是缺乏状态的独特特征。相反，膳食补充（n-3）脂肪酸导致（n-3）脂肪酸显著增加，尤其是20:5（n-3）。关于两种饮食的抗炎作用，EFA缺乏而非（n-3）脂肪酸补充会使腹腔常驻巨噬细胞水平降低。在抑制酵母聚糖刺激下多形核中性粒细胞的流入方面，EFA缺乏也比（n-3）脂肪酸补充更有效。两种饮食对体内白三烯（LT）B生成的影响也明显不同。EFA缺乏完全抑制LTB的合成。相比之下，膳食补充（n-3）脂肪酸仅使LTB4的产生减少50%。补充（n-3）脂肪酸时会产生LTB5。（n-3）脂肪酸补充在减少LTB4生成方面作用较小并非由于环氧化酶途径受阻。EFA缺乏而非（n-3）脂肪酸补充与血栓素合成减少有关。尽管膳食脂肪酸调节已被证明可减少血小板活化因子（PAF）合成，但使用PAF受体阻滞剂L659989的研究表明，在该炎症模型中PAF并非引发白细胞的重要因素。总之，在急性炎症中，EFA缺乏的抗炎作用比膳食补充（n-3）脂肪酸更显著。这种抗炎潜力的差异似乎是由于EFA缺乏在降低腹腔常驻巨噬细胞水平或抑制体内LTB4生成方面具有更大作用。
