Age Associated Alterations in Costimulatory and Adhesion Molecule Expression in Lupus-Prone Mice Are Attenuated by Food Restriction with n-6 and n-3 Fatty Acids

Abstract

Costimulatory and adhesion molecules are known to play a major role in the pathogenesis of systemic lupus erythematosus. Since fish oil and calorie restriction have been reported to attenuate the development of disease in lupus prone (NZBxNZW)F1 mice, the objective of this study was to assess the expression of these key inflammatory molecules in these mice fed diets differing in n-6 and n-3 fatty acid content and fed either food restricted or ad libitum. Age-associated increases in the expression of CD28, ICAM-1, and PGP-1 molecules that are involved in the recruitment of inflamed lymphocytes into the kidney were attenuated in mice restricted in food intake. The increase in costimulatory (CD80 and CD86) and adhesion (ICAM-1, PGP-1, LFA-1, and Mac-1) in peripheral blood mononuclear cells was also attenuated by food restriction and to a lesser extent by fish oil alone. Interestingly, amelioration of lupus (laminin expression and proteinuria) correlated with the above beneficial effects and could be seen even in 24-month-old mice. In summary, food restriction and fish oil delay the onset of lupus disease and increase life span in B/W mice by prolonging the maintenance of a youthful immune phenotype.

Anti-inflammatory action of dietary fish oil and calorie restriction

“…In our previous work (Kim et al, 2005), we reported that FO feeding enhanced antioxidant enzyme activity, and this might be the underlying reason that how highly oxidizable FO is able to reduce lipid peroxidation as shown in this current study. In addition, the synergistic effects of dietary FO and CR that we found in the current study are consistent with previous studies that show their combined use is more effective in the modulation of antioxidant enzymes and the extension of life span (Jolly et al, 2001;Muthukumar et al, 2003Muthukumar et al, , 2004), compared to the use of CR or dietary FO alone (Lim et al, 2000).…”

A randomised interventional trial of -3-polyunsaturated fatty acids on endothelial function and disease activity in systemic lupus erythematosus

“…However, many of these studies employed animal models18 – 21 or used high-dose n-3 PUFAs30 – 33 (up to 20 g/day), which would be difficult for patients to consume on a regular basis or to achieve through dietary means. This study confirms the finding of a previous study by our group that showed low-dose n-3 PUFAs have beneficial effects on disease activity in patients with SLE 22…”

“…In murine models of SLE, modulation of fatty acid metabolism by increasing n-3 PUFAs intake can result in a therapeutic effect 18 – 21. High-dose (20 g daily) n-3 PUFAs has been shown to improve clinical features of SLE and our group has also previously shown a reduction in SLE disease activity with low-dose n-3 PUFAs 22…”

Intracellular metabolic pathways control immune tolerance

“…Indeed, dietary restriction causes metabolic and physiological changes that have beneficial effects against obesity, insulin resistance, inflammation, oxidative stress and cardiovascular diseases [66][67][68][69]. It has recently been shown that changes in nutritional status of the host can directly affect survival and proliferation of autoreactive CD4 + T cells through leptin, which modulates Bcl-2 activity, production of both Th1 and Th17 cytokines, and the nutrient/ energy-sensing AKT-mTOR pathway [70].…”