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VITAMIN A, INFECTION, AND
IMMUNE FUNCTION*
Key Words retinoic acid, immunity, T-cells, acute phase response
* Abstract In populations where vitamin A availability from food is low, infectious diseases can precipitate vitamin A deficiency by decreasing intake, decreasing absorption, and increasing excretion. Infectious diseases that induce the acute-phase response also impair the assessment of vitamin A status by transiently depressing serum retinol concentrations. Vitamin A deficiency impairs innate immunity by impeding normal regeneration of mucosal barriers damaged by infection, and by diminishing the function of neutrophils, macrophages, and natural killer cells. Vitamin A is also required for adaptive immunity and plays a role in the development of both T-helper (Th) cells and B-cells. In particular, vitamin A deficiency diminishes antibody-- mediated responses directed by Th2 cells, although some aspects of Th1-mediated immunity are also diminished. These changes in mucosal epithelial regeneration and immune function presumably account for the increased mortality seen in vitamin A-- deficient infants, young children, and pregnant women in many areas of the world today.
INTRODUCTION
Physicians and nutritionists have long known that malnutrition increases the severity of infection and that serious or repeated infections increase the risk of malnutrition (91). This is certainly true of vitamin A. In 1928, not long after its identification (62,74), vitamin A was termed "the anti-infective vitamin" (43). This description was not entirely accurate, however, as more recent work has shown that vitamin A does more to enhance recovery from infection than it does to prevent infection in the first place. Perhaps in recognition of this fact, the therapeutic use of vitamin A became an area of great research interest during the 1930s (for a review, see 94). The advent of antibiotics in the 1940s dampened interest in this area for many years, but interest was rekindled in the 1980s, when the critical role of vitamin A in preventing mortality from infectious diseases was demonstrated anew in clinical and community studies (51, 111). Mechanistic research on the role of vitamin A at the cellular and molecular level also received a substantial boost in the 1980s, when the nuclear receptors for the vitamin A metabolites all-trans and 9-cis retinoic acid (RA) were discovered (41a, 59,76). These receptors regulate gene transcription and include the...