It is well established that immune responses tend to decrease as humans and animals enter old age. The role of the chronic diet may play in modulating age-related changes in immune functions is not well understood. Vitamin A (retinol) status may be particularly pertinent because of the demonstrated effects of retinoids on cellular growth, differentiation and function. The investigator proposes to use the Fischer 344 rat as a model of aging to explore the effects of chronic diet on two major aspects of immune function: antibody production elicited by pneumococcal polysaccharide, a clinically important antigen in the aged population, and natural killer (NK) cell function, an aspect of antibody-independent immunity implicated in tumor surveillance and in regulation of the antibody responses. The first two specific aims will establish (1) appropriate doses of antigen and timing of antibody production to pneumococcal polysaccharide in rats of various ages, and (2) appropriate dietary conditions to maintain rats in a chronic marginal vitamin A status or a retinol-abundant status.
Specific aim 3 is designed to address the following questions: Does a chronic diet that is marginal in vitamin A exacerbate the age-related decrease in immune functions? Will chronic dietary supplementation with vitamin A significantly increase (or possibly suppress) immune responses? Animals will be studied at four ages so as to compare the responses of young, adult, """"""""aging"""""""" and elderly animals.
In Aim 4, the investigator will determine whether the retinol-enriched diet has deleterious effects, e.g., on serum lipid concentrations or liver function. The goal of Aim 5 is to determine whether administration of retinol acutely can overcome the immunosuppressive effects of age in animals fed a diet chronically marginal in retinol.
Aim 6 will explore the hypothesis that vitamin A affects immune functions, at least in part, through its action on macrophages and/or NK cells via the soluble factors they elaborate. The investigators will conduct a series of mechanistic studies focused on the response to lipopolysaccharide and lymphokines or cytokines, particularly interleukin-1B, tumor necrosis factor-alpha, and immune interferon which may regulate the antibody response to pneumococcal polysaccharide and/or cytotoxicity by NK cells. In all, the proposed investigations will help to understand the role of chronic diet in the immune response to infectious disease and in natural immunity throughout the life span.
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