NUTRITION AND AGING--VITAMIN A AND IMMUNE FUNCTIONS

Project: Research project

Description

DESCRIPTION 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.
StatusFinished
Effective start/end date6/1/911/31/97

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Vitamin A
Diet
Natural Killer Cells
Polysaccharides
Vitamins
Antibody Formation
Research Personnel
Antigens
Lymphokines
Retinoids
Inbred F344 Rats
Dietary Supplements
Innate Immunity
Interferon-alpha
Interferon-gamma
Young Adult
Immunity
Tumor Necrosis Factor-alpha
Cytokines
Antibodies