TNO Quality of Life, PO Box 360, 3700 AJ Zeist, the Netherlands.
BMC Med Genomics. 2010 Feb 23;3:5. doi: 10.1186/1755-8794-3-5.
Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately describe the complexity of metabolic responses to mild anti-inflammatory therapy.
To address this limitation, we used an integrative omics approach to characterize modulation of inflammation in overweight men during an intervention with the non-steroidal anti-inflammatory drug diclofenac. Measured parameters included 80 plasma proteins, >300 plasma metabolites (lipids, free fatty acids, oxylipids and polar compounds) and an array of peripheral blood mononuclear cells (PBMC) gene expression products. These measures were submitted to multivariate and correlation analysis and were used for construction of biological response networks.
A panel of genes, proteins and metabolites, including PGE2 and TNF-alpha, were identified that describe a diclofenac-response network (68 genes in PBMC, 1 plasma protein and 4 plasma metabolites). Novel candidate markers of inflammatory modulation included PBMC expression of annexin A1 and caspase 8, and the arachidonic acid metabolite 5,6-DHET.
In this study the integrated analysis of a wide range of parameters allowed the development of a network of markers responding to inflammatory modulation, thereby providing insight into the complex process of inflammation and ways to assess changes in inflammatory status associated with obesity.
The study is registered as NCT00221052 in clinicaltrials.gov database.
肥胖人群中慢性全身性低度炎症与包括心血管疾病、胰岛素抵抗和糖尿病在内的健康并发症有关。降低炎症反应可能会降低这些风险。然而，现有的炎症状态标志物并不能充分描述对轻度抗炎治疗的代谢反应的复杂性。
为了解决这一局限性，我们采用了一种综合组学方法来描述超重男性在使用非甾体抗炎药双氯芬酸干预期间炎症的调节。测量的参数包括 80 种血浆蛋白、>300 种血浆代谢物（脂质、游离脂肪酸、氧化脂质和极性化合物）以及一系列外周血单核细胞（PBMC）基因表达产物。这些测量值进行了多元和相关分析，并用于构建生物反应网络。
确定了一组基因、蛋白质和代谢物，包括 PGE2 和 TNF-α，这些基因、蛋白质和代谢物描述了双氯芬酸反应网络（PBMC 中的 68 个基因、1 种血浆蛋白和 4 种血浆代谢物）。炎症调节的新型候选标志物包括 PBMC 中 annexin A1 和 caspase 8 的表达以及花生四烯酸代谢物 5,6-DHET。
在这项研究中，对广泛参数的综合分析允许开发一个响应炎症调节的标志物网络，从而深入了解炎症的复杂过程以及评估与肥胖相关的炎症状态变化的方法。
该研究在 clinicaltrials.gov 数据库中注册为 NCT00221052。
