Jaudszus Anke, Krokowski Martin, Möckel Peter, Darcan Yasemin, Avagyan Anzhela, Matricardi Paolo, Jahreis Gerhard, Hamelmann Eckard
Institute of Nutrition, Friedrich Schiller University, 07743 Jena, Germany.
J Nutr. 2008 Jul;138(7):1336-42. doi: 10.1093/jn/138.7.1336.
Milk consumption from early childhood on has been found to be inversely correlated with allergic sensitization and the onset of bronchial asthma. We tested whether cis-9,trans-11-conjugated linoleic acid (c9,t11-CLA), naturally occurring in milk fat, may prevent allergic sensitization and inhibit airway inflammation in a murine asthma model. BALB/c mice were fed a diet enriched in 1 wt% of c9,t11-CLA or a control diet 7 d prior to and for 32 d during sensitization [d 1 and 14, 100 mg/L ovalbumin (OVA) in adjuvant vs. PBS] and airway challenges (d 28-30, 1% OVA in PBS vs. PBS). Subgroups of mice were coadministered 20 micromol/L of the selective PPARgamma antagonist GW9662 during each OVA challenge. C9,t11-CLA feeding resulted in significantly reduced IgE production and allergen-induced in vivo airway hyperresponsiveness. Further, less mucous plugging of segmental bronchi and significantly reduced interleukin-5 and eosinophils were determined in bronchoalveolar lavage fluids of c9,t11-CLA-fed mice. C9,t11-CLA feeding prevented the downregulation of PPARgamma mRNA in the lung tissues observed after allergen sensitization and airway challenges in control mice. The inhibitory effects of c9,t11-CLA on airway inflammation were partially prevented by coadministration of GW9962. Further, c9,t11-CLA feeding resulted in a significantly lower concentration of the eicosanoid precursor, arachidonic acid, in tissue lipids. These findings demonstrate that dietary c9,t11-CLA can reduce allergic airway inflammation, most likely via a PPARgamma-related mechanism and by reducing eicosanoid precursors. They give new insights into the fatty acid-mediated mechanism of immunomodulation and may represent a step toward an attractive novel strategy in the dietary prevention and treatment of allergic asthma.
研究发现，从幼儿期开始饮用牛奶与过敏致敏及支气管哮喘的发病呈负相关。我们测试了乳脂肪中天然存在的顺-9，反-11-共轭亚油酸（c9，t11-CLA）是否能在小鼠哮喘模型中预防过敏致敏并抑制气道炎症。在致敏前7天及致敏期间32天（第1天和第14天，佐剂中含100 mg/L卵清蛋白（OVA）与磷酸盐缓冲液（PBS）对比）以及气道激发试验期间（第28 - 30天，PBS中含1% OVA与PBS对比），给BALB/c小鼠喂食富含1 wt% c9，t11-CLA的饮食或对照饮食。在每次OVA激发试验期间，给小鼠亚组共同施用20 μmol/L的选择性过氧化物酶体增殖物激活受体γ（PPARγ）拮抗剂GW9662。喂食c9，t11-CLA导致IgE产生显著减少以及变应原诱导的体内气道高反应性降低。此外，在喂食c9，t11-CLA的小鼠支气管肺泡灌洗液中，节段性支气管的黏液堵塞减少，白细胞介素-5和嗜酸性粒细胞显著减少。喂食c9，t11-CLA可防止对照小鼠在变应原致敏和气道激发试验后肺组织中PPARγ mRNA的下调。共同施用GW9962可部分阻止c9，t11-CLA对气道炎症的抑制作用。此外，喂食c9，t11-CLA导致组织脂质中类二十烷酸前体花生四烯酸的浓度显著降低。这些发现表明，饮食中的c9，t11-CLA可减轻过敏性气道炎症，最有可能是通过与PPARγ相关的机制并通过减少类二十烷酸前体来实现。它们为脂肪酸介导的免疫调节机制提供了新的见解，可能代表了饮食预防和治疗过敏性哮喘的一种有吸引力的新策略的一个步骤。
