Recent studies indicate that an excessive inflammatory response is etiologically related to the pathogenesis of age-related macular degeneration (AMD). Epidemiologic studies suggest that dietary lutein and zeaxanthin intake is inversely associated systemic inflammation and risk for AMD. The objective of this work is to directly determine the effects of lutein and zeaxanthin supplementation on ocular and systemic inflammatory response. ARPE-19 cells and primary murine macrophages were cultured in the presence of 0, 1 and 10 μM lutein or zeaxanthin for 1–3 days and then stimulated with lipopolysaccharide (LPS) in fresh medium for 8 h. Levels of IL-6, IL-8 and TNFα in the medium were determined by ELISA and used as indicators of inflammatory response. To test the anti-inflammatory effects of lutein/zeaxanthin in vivo, C57BL mice were fed diets containing 0, 0.02%, and 0.1% lutein or zeaxanthin for 3 months. Macrophages were isolated from peritonea and cultured in the presence of LPS for 16 h. Levels of IL-6 and TNFα in the medium were determined. Cultured RPE produced relatively high levels of IL-6 and IL-8 even in the absence of LPS, but levels of IL-6 and TNF〈 secreted by macrophages in resting state were barely detectable. Treatment of RPE and macrophages with LPS resulted in a dramatic increase in production of IL-6, IL-8, and TNFα. Supplementation with lutein suppressed LPS-stimulated production of these inflammatory mediators in both RPE and macrophages. These suppressive effects were dose dependent. Lutein supplementation to cultured RPE also suppressed the production of IL-6 and IL-8 in the absence of LPS stimulation. Furthermore, macrophages isolated from lutein-supplemented mice produced less IL-6 and TNFα upon LPS stimulation and the suppressive effects were also dose dependent. Supplementation with zeaxanthin suppressed the production of IL-8, but not IL-6. These data indicate that lutein and zeaxanthin have anti-inflammatory effects and that increased dietary lutein or zeaxanthin intake may reduce the risk for AMD via modulating ocular and systemic inflammation.
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We thank Kemin Industries and ZeaVison for providing lutein and zeaxanthin for dietary supplementation experiments. This work is supported by USDA AFRI Award 2009-35200-05014, NIH grant EY 011717, USDA contract 1950-510000-060-01A, and Dennis L. Gierhart Charitable Gift.
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