Immune-modulating effects of CLA have been reported in animals, but results are inconsistent. In humans, CLA has shown no effects or only minor effects on immune function. The objective of this study was to evaluate the immune-modulating effects of 3 g cis-9,trans-11 (c9,t11) vs. trans-10,cis-12 (t10,c12) CLA isomers in a population with a high risk of coronary heart disease characterized by moderate overweight (body-mass index, 25-32.5 kg/m2) in combination with LDL-phenotype B (> or = 35% small LDL cholesterol, density > or = 1.040 g/mL). After a run-in period of 1 wk, 42 men and women were randomly allocated to the c9,t11 CLA group, the t10,c12 CLA group, or the placebo group. Effects of 13 wk of consumption of 3 g of CLA isomers on cytokine production by ex vivo lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) and whole blood, and on plasma C-reactive protein (CRP) concentrations were evaluated. To generate hypotheses for future studies, protein expression patterns of 42 cytokines, chemokines, and growth factors were evaluated with an antibody array in pooled, nonstimulated, fasting plasma samples. LPS induced interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha production by PBMC, and whole blood as well as plasma CRP concentrations were not significantly changed by the c9,t11 and the t10,c12 CLA isomers. The cytokine expression profile in nonstimulated plasma suggested that both CLA isomers induced a specific inflammatory signature, in which the c9,t11 CLA group showed more activity in terms of numbers of proteins regulated. We conclude that daily consumption of 3 g of c9,t11 or t10,c12 CLA isomer did not affect LPS-stimulated cytokine production by PBMC or whole blood and plasma CRP levels. Inflammatory signatures in fasting, nonstimulated plasma as determined by an antibody array may indicate enhanced immune function by both CLA isomers. AD - Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, The Netherlands.