Vitamin A Status: Relationship to Immunity and the Antibody Response

Abstract

Vitamin A (retinol and its derivatives) is essential for a variety of biologic processes, many of which are related to growth, cellular differentiation, and cell-cell or cell-substrate interactions. Within the last 5 years, there has been a renaissance of interest in vitamin A and immunity that is based largely on three important advances. First, a number of controlled, field-based or hospital-based, studies have demonstrated that vitamin A supplementation can decrease mortality in preschool children in populations at high risk for vitamin A deficiency. Although a mechanistic link between child survival and improved immunity has yet to be established, it seems quite probable that at least some of the benefit of vitamin A is due to restoration of epithelial barriers and improved resistance to respiratory and gastrointestinal infections. Second, vitamin A, either in the form of retinol or its metabolite, retinoic acid, has been shown to stimulate the rejection of certain immunogenic tumors; this effect may be due to enhanced immunologic surveillance. Third, there has been a swell of interest in vitamin A's mechanism of action in nearly all organ systems as the result of the identification of nuclear receptors for retinoic acid and, consequently, advances in understanding the role of retinoic acid in gene regulation.

Vitamin A deficiency, even in relatively early stages, is associated with impairment of linear growth, cartilage, and bone development and changes in epithelial cell differentiation and function (1). If vitamin A deficiency is allowed to persist, animals either succumb or, if they survive, develop progressive xerophthalmia leading to blindness. In parts of the developing world, particularly Southeast Asia and sub-Saharan Africa, xerophthalmia remains a significant, and preventable, public health problem (2).

Both clinical and experimental evidence has shown that vitamin A deficiency is associated with decreased resistance to infection. Vitamin A deficiency could affect immunity through a number of mechanisms including (i) changes in lymphopoiesis and lymphocyte maturation, (ii) abnormal cytokine production, (iii) altered membrane structure affecting receptors for antigens, accessory molecules, or cytokines, (iv) increased penetration of bacteria, vires, and parasites through epithelial barriers, and (v) impaired clearance of pathogens by cytotoxic and phagocytic mechanisms.