Insight in modulation of inflammation in response to diclofenac intervention: a human intervention study

• Published in: BMC medical genomics 2010-02, Vol.3 (1), p.5-5, Article 5
• Main Authors: van Erk, Marjan J, Wopereis, Suzan, Rubingh, Carina, van Vliet, Trinette, Verheij, Elwin, Cnubben, Nicole H P, Pedersen, Theresa L, Newman, John W, Smilde, Age K, van der Greef, Jan, Hendriks, Henk F J, van Ommen, Ben
• Format: Article
• Language: English
• Subjects: Adult; Annexin A1 - genetics; Annexin A1 - metabolism; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Arthritis; Body Mass Index; Cardiovascular disease; Caspase 8 - genetics; Caspase 8 - metabolism; Colleges & universities; Data analysis; Diabetes; Diclofenac; Diclofenac - therapeutic use; Dinoprostone - blood; Dosage and administration; Drug therapy; Family medical history; Gene Expression Profiling; Genetic aspects; Humans; Inflammation; Inflammation - genetics; Inflammation - metabolism; Inflammation Mediators - metabolism; Insulin resistance; Male; Metabolism; Metabolites; Metabolomics; Middle Aged; Multivariate Analysis; Nutrition research; Obesity; Obesity - drug therapy; Obesity - genetics; Obesity - metabolism; Overweight; Plasma; Proteins; Proteomics; Quality of life; Research article; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1755-8794; 1755-8794
• 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.