n-3 PUFA in CVD: influence of cytokine polymorphism.

In their current guidelines cardiac societies recommend the consumption of the two n-3 fatty acids EPA and DHA to prevent cardiovascular complications. Cardiovascular events are reduced by EPA and DHA, because they are antiarrhythmic, mitigate the course of atherosclerosis and stabilise plaque. As atherosclerosis is considered an inflammatory disorder a number of studies have investigated the anti-inflammatory mechanisms of EPA and DHA in a cardiovascular context in human dietary intervention studies. Pro-inflammatory cytokines, or cytokines reflecting inflammatory processes, e.g. IL-1beta, IL-2, IL-6, TNFalpha, platelet-derived growth factor (PDGF)-A and -B and monocyte chemoattractant protein-1 (MCP-1), are reduced by ingestion of EPA and DHA by human subjects. Interestingly, C-reactive protein remains largely unaltered. However, in in vitro and animal models, but less so in human subjects, soluble cytokines reflecting interactions between blood cells and the vessel wall, such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, are reduced. Moreover, in contrast to common expectations, oxidative stress seems to be reduced after ingestion of EPA and DHA, at least as indicated by measurement of urinary F(2) isoprostane excretion. Notably, for PDGF-A and -B and for MCP-1 the reduction has been demonstrated to occur at the gene expression level, which indicates that a deliberate change in diet can alter gene expression quantitatively. The precise underlying mechanism, however, remains to be clarified, but might involve PPAR, NF-kappaB and/or the eicosanoid system. The same holds true for the mechanisms by which levels of other cytokines are altered by EPA and DHA.