|Dao, Maria Carlota|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/29/2010
Publication Date: 7/1/2010
Citation: Ren, Z., Pae, M., Dao, M., Smith, D., Meydani, S., Wu, D. 2010. Dietary supplementation with tocotrienols enhances imune functiuon in C57BL/6 mice. Journal of Nutrition. 140:1335-1341. Interpretive Summary: As people age, their immune responses decline; therefore, the elderly are susceptible to having a higher incidence of infections and cancer. The use of nutritional intervention is a practical approach to strengthen the immune system. In a number of animal and human studies, we and others have established that one kind of vitamin E (alpha-tocopherol or a-Toc) can enhance the function of the immune system. In contrast, tocotrienols (T3), the other half of natural vitamin E family, have not been well studied; therefore, we studied their ability to improve the immune response. In this study, young (4 mo) and old (23 mo) mice were pair-fed a diet supplemented with T3 for 6 weeks and found feeding T3 resulted in an enhanced T cell proliferation, a measure of T cell function, the cells involved in fighting against viruses and bacteria. Using individual T3 isomers (different forms of T3) in the in vitro (“test tube”) experiments, we found that all the T3 tested are capable of promoting T cell proliferation but with different effectiveness. Like a-Toc, T3 enhance T cell proliferation more dramatically in old mice. These data show for the first time that T3 enhances T cell function particularly in both young and old mice but more effectively in old mice compared to young. These findings would suggest that T3 might improve immune response, particularly in the aged.
Technical Abstract: Aging is associated with decline in immune response, which pre-disposes the elderly to higher incidence of infections and cancer. Nutritional intervention is a practical approach to favorably modulate immune function. We and others have established that vitamin E (alpha-tocopherol, a-Toc) can enhance T cell-mediated immune function in a number of animal and human studies. In contrast, tocotrienols (T3), the other half of natural vitamin E family, are much less studied in general and in particular, little is known as to whether they modulate immune function. In this study, young (4 mo) and old (23 mo) C57BL/6 mice were pair-fed a diet supplemented with 500 mg/kg Tocomin (Trademark) 50 percent, a mixture of all 4 types of T3 and a-Toc or a diet containing equal amount of a-Toc to that in Tocomin diet for 6 wk. As expected, lymphocyte proliferation was lower in old mice compared to young mice. Lymphocyte proliferation in old T3 group was significantly higher than that seen in old control group at all stimulation conditions and this effect was much less significant in old mice. Splenocytes from old mice produced less IL-2, IL-4, and IL-6 compared to young mice while no significant age-related difference was found in IL-1beta, TNF-alpha, IFN-gamma, and IL-10. T3 feeding increased IL-1beta and tended to increase IL-2 production in old mice but not in young mice. Peritoneal macrophages from old mice produced significantly more IL-1beta, IL-6, IL-10, and PGE2 compared to those from young mice and T3 feeding increased IL-1beta production in both young and old mice. In vitro supplementation study using individual T3 showed that all the T3 tested enhanced Con A-stimulated lymphocyte proliferation with a potency order of alpha-> gamma-> delta-T3, at range 0.01 to 5 micromol/L with maximal enhancement reached at 0.15, 0.3, and 0.625 micromol/L, respectively. Similar to the finding in the feeding study, this effect is more significant in old than in young mice mainly depending on the basal proliferation levels. Future studies will investigate the mechanisms for this effect of T3.