Lutein Supplementation Suppresses Inflammatory Responses in Retinal Pigment Epithelial Cells (RPE) and Macrophage

Abstract

Purpose: : Recent studies indicate that excessive inflammatory responses are etiologically related to the pathogenesis of age-related macular degeneration (AMD). Epidemiologic studies suggest that dietary lutein intake is inversely associated systemic inflammation and risk for AMD. The objective of this work is to directly determine the effects of lutein supplementation on ocular and systemic inflammatory response.

Methods: : To determine the effects of lutein supplementation on inflammatory responses, ARPE-19 cells or primary marine macrophage were cultured in the presence of 0, 1 and 10 uM lutein for 2 days. Lipopolysaccharide (LPS) was used to trigger inflammatory response. Levels of IL-6, IL-8 and TNFα in the medium were determined ELISA and used as indicators of inflammatory response. Levels of lutein in the cells were determined using an HPLC method. To test the antii-inflammatory effects in vivo, C57BL/6 mice were fed diets containing 0%, 0.02% and 0.1% lutein for 3 months. Levels of lutein in serum and liver were determined. Macrophage were isolated from peritonea and cultured in presence of LPS for 8 and 24 h. Levels of in IL-6 and TNF-α in the medium were detected by ELISA.

Results: : RPE accumulated lutein upon supplementation. The concentrations of lutein in RPE were ~5 fold of those in the medium upon 2 days of supplement incubation. Treatment of RPE and macrophage with LPS resulted in a dramatic >100-fold increase in the production of IL-6, IL-8 and TNF-α. Supplementation of lutein suppressed LPS-stimulated production of these inflammatory mediators in both RPE and macrophages. These suppressive effects are dose-dependent. Furthermore, dietary supplementation of lutein resulted in a dose-dependent accumulation of lutein in serum and livers. Macrophages isolated from lutein supplemented mice produced less IL-6 and TNF-α upon LPS stimulation and these suppressive effects were also dose-dependent.

Conclusions: : These data indicate that lutein has an anti-inflammatory effect and that increased dietary lutein intake may reduce the risk for AMD via modulating ocular and systemic inflammation.

Keywords: inflammation • protective mechanisms • cytokines/chemokines