Nutritional modulation of immune responses.

Malnutrition has been linked in field studies with increased susceptibility to infection, often associated with severe marasmus or kwashiorkor. However, studies by Jose and colleagues revealed an apparent paradox: while B-cell immunity was decreased by chronic moderate malnutrition, several aspects of T-cell immunity were enhanced. In extensive experimental studies we have analyzed the effects of dietary restriction in immunologic function and development of disease. Our investigations may be grouped into three related areas. 1) Differential effects of protein or protein-calorie malnutrition on B-cell and T-cell immunity. While antibody-mediated immunity was impaired in animals moderately restricted with respect to protein or total calories, several T-cell functions were consistently enhanced in mice, rats, guinea pigs, and monkeys. 2) Influence of restricting a single nutritional element, the trace metal zinc, on immunologic function. Zinc deficiency produces progressive thymic involution and a progressive loss of T-cell immunity functions in mice and rats. While congenital failure to absorb this element normally is the single cause of hereditary acrodermatitis enteropathica, a frequently lethal disease both in humans and in cattle, acrodermatitis enteropathica has also been linked with common variable immunodeficiency disease, total parenteral alimentation with preparations lacking zinc, several forms of cancer, marasmus, and kwashiorkor. 3) Inhibition by dietary restriction of development of the diseases of aging. Disorganization of thymus-derived immunity, and development with aging of genetically determined diseases in several strains of mice, can be sharply curtailed or even prevented by reducing the intake of total calories or fat. Similarly, development of mammary cancer in C3H female mice is prevented by restricting dietary intake of fat.