Project Number: 5306-51530-018-00
Project Type: Appropriated

Start Date: Jan 18, 2009
End Date: Jan 17, 2014

Objective:
Objective 1: Conduct a controlled, vitamin D supplementation trial in volunteers with vitamin D insufficiency (VDI) to determine if supplementation to achieve the proposed level of >75 nmol/L for maintenance of bone health is also appropriate for maintenance of immune function. ¿ Sub-objective 1A. Determine if supplements decrease the production of proinflammatory and increase the production of anti-inflammatory cytokines and chemokines by innate immune cells stimulated ex vivo. ¿ Sub-objective 1B. Determine if supplements decrease serum markers of inflammation and autoimmune activity, and increase serum levels of defensive molecules. ¿ Sub-objective 1C. Determine if supplements decrease blood levels of proinflammatory T-helper type 1 (Th1) and Th17 cells and increase levels of anti-inflammatory T-regulatory (Treg) and Th2 cells. Objective 2: Determine the impact of plant polyphenols and polyphenol-rich foods on immune cell function using cell culture systems, mouse models, and human volunteers. Examine anti-inflammatory and anti-cancer activities of polyphenols in animal models, as well as inflammation and oxidative damage in studies with human volunteers, including overweight/obese individuals. ¿ Sub-objective 2A. Analyze the effects of polyphenol-rich foods and individual plant polyphenols on immune cell function in vivo and ex vivo. ¿ Sub-objective 2B. Examine anti-inflammatory activities of polyphenol-rich foods, individual plant polyphenols and vitamin A in mice and humans who are at risk for developing inflammatory disease, such as autoimmune mice and obese humans. ¿ Sub-objective 2C. Evaluate the anti-cancer activity of polyphenol-rich foods and individual plant polyphenols. Objective 3: Examine the absorption of '-cryptoxanthin (CX) from supplements and foods, its contribution to vitamin A stores, and the impact of CX, other carotenoids and vitamin A on immune function. ¿ Sub-objective 3A. Measure the absorption and metabolism of CX from Satsuma mandarin juice fed to healthy adult humans. ¿ Sub-objective 3B. Estimate the impact of daily consumption of food sources of CX or '-carotene (BC) on plasma and breast milk concentrations of CX, BC and retinol in lactating women. ¿ Sub-objective 3C. Determine the impact of CX on immune and bone marker status in the Mongolian gerbil. Objective 4: Determine if high-level vitamin A intake is associated with higher Th2 and Treg responses and lower Th1 and Th17 responses relative to adequate and deficient intake. ¿ Sub-objective 4A. Using dietary and targeted gene disruption approaches in mice, determine if vitamin A enhances Th2 and Treg responses by acting directly on T cells. ¿ Sub-objective 4B. Using subjects recruited in the vitamin D supplementation trial described under Objective 1, determine if vitamin A status is associated with higher blood levels of NK, NK-T, Th2 and Treg cells, and lower levels of Th1 and Th17 cells.

Approach:
The impact of vitamins A and D, and plant polyphenols, on immune function will be examined using cell culture systems, mouse models, and human intervention trials. The anti-cancer activities of polyphenols will be examined in animal models. Absorption of beta-cryptoxanthin will be examined in gerbils and humans. Replacing 5306-51530-013-00D (1/09).