Effects of dietary ω3 and ω6 lipids and vitamin E on chemokine levels in autoimmune-prone MRL/MpJ- lpr/lpr mice

Abstract

Elevated levels of chemokines, such as Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES), Monocyte Chemotactic Protein-1 (MCP-1), Macrophage Inflammatory Protein-1α (MIP-1α), and Macrophage Inflammatory Protein-1β (MIP-1β) have been found in rheumatoid arthritis (RA) and juvenile arthritis (JA), and they may be associated with the pathogenesis of these diseases. These chemokines are implicated in the migration of specific leukocytes into the joints. Omega-3 (ω3) fatty acid rich-fish oil (FO) and vitamin E may delay the progress of certain autoimmune diseases. The present study was designed to understand the effects of dietary lipids (ω-6 and ω-3 fatty acids) and vitamin E on the production of chemokines in autoimmune-prone MRL/ lpr (a mouse model for RA) and congenic control MRL/++ mice. The MRL mice were fed for 4.5 months ω-6 and ω-3 diets that varied in lipid sources (corn oil; CO and fish oil; FO) and vitamin E levels (269 I.U./kg and 694 I.U./kg diet). Spleen cells were isolated and cultured aseptically in the presence of PHA for 48 h at 37°C and the levels of chemokines (RANTES, JE/MCP-1 and MIP-1α) were determined in the cell-free supernatants. The levels of RANTES and JE/MCP-1 were significantly higher in MRL/ lpr mice compared to MRL/++ mice. The FO had differential effect on RANTES and MCP-1 production by spleen cells. The production of RANTES and JE/MCP-1 by spleen cells in mice fed the FO diets was significantly lower than in mice fed the CO diets ( p < 0.0001). The levels of vitamin E did not affect the production of RANTES and JE/MCP-1. The levels of vitamin E had a significant effect on MIP-1α as the spleen cells of mice fed diets containing 694 IU/kg diet of vitamin E produced significantly higher levels of MIP-1α compared to the group of mice fed the diets containing 269 IU of vitamin E ( p < 0.0001). The data obtained from this study in MRL/ lpr and MRL/++ mice suggest that FO diets containing ω-3 fatty acids are beneficial in decreasing the levels of certain pro-inflammatory chemokines (RANTES and MCP-1) thereby delaying the onset of and severity of autoimmune symptoms in MRL/ lpr mouse model.