SO1 Nutritional Modulation of Immune Function

Polyphenols and isoflavones exert multiple effects in cellular metabolism from signaling pathways to the regulation of gene expression and profoundly influence cellular function. The anti-inflammatory properties of various polyphenols – isomers and derivatives of resveratrol, piceatannol – and the isoflavone genistein have been analyzed in cell-based assays. Both groups of substances potently abrogated cyclooxygenase (COX)-2 dependent prostaglandin (PG) E2 production by lipopolysaccharide-stimulated macrophage cell line RAW264.7 with similar IC50 values (3 microM). Likewise, resveratrol – but not genistein – inhibited PGE2 production in human monocyte/macrophage THP1 cells. Both substances significantly reduced nitric oxide (NO) production (IC50 20 microM) in RAW264.7 cells. We have also evaluated the effects of combination of resveratrol and genistein on the two inflammatory parameters. Their mode of action was in part mediated by the NFB signaling pathway. Polyphenols and isoflavones reduced the mRNA levels of LPS-induced proinflammatory cytokines (e.g. IL-1alpha, IL-1beta, IL-6, IL-8, TNFalpha), COX-2, and iNOS as determined by quantitative RT-PCR analyses. Gene microarray analysis corroborated these data and further revealed that numerous genes of the inflammatory pathways (e.g. interferonand cytokine-related genes and their receptors) were modulated by resveratrol and genistein, with each substance displaying an idiosyncratic regulation pattern. The results indicate that representatives of both groups of substances of the natural food chain have various potent effects on cellular parameters of inflammation and affect different pathways in stimulated macrophages. Therefore, they should further be considered as food ingredients for preventing or modulating a variety of factors related to clinical conditions where inflammatory processes are involved. SO1.2 Energy Restriction Restores Altered Immune Response in Previously Diet-Induced (Cafeteria Diet) Overweight Rats