EFFECT OF ZINC ON IMMUNOCOMPETENCE IN THE ELDERLY

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This application addresses the hypothesis that differences in dietary zinc content and zinc nutriture may affect the immune response in the elderly. We further hypothesize that the mechanism of improvement in the immune response is both a correction of underlying zinc deficiency and a pharmacologic (drug) effect of high doses of zinc, with the latter effect being more important for most patients. The subjects of this study will be elderly adults who will be divided into 3 groups based on an initial determination of their plasma zinc concentration (less than 60 ug/dl, 60-80 ug/dl, or greater than 80 ug/dl). Subjects from the 3 groups will be randomly assigned to one of three treatments: 15 mg Zn daily, 100 mg Zn daily, or a placebo. Administration of Zn or placebo will continue for one year. Blood and hair samples will be collected at 0, 3, 6, 12, and 24 months after beginning zinc administration. The following tests will be done to assess subject zinc nutriture: plasma Zn, hair Zn, plasma alkaline phosphatase, serum albumin, and erythrocyte zinc. Immunocompetence will be assessed by several methods, including evaluation of delayed dermal hypersensitivity, in vitro response of lymphocytes to mitogens and antigens, assessment of lymphocyte surface markers, and evaluation of natural killer cell function. Subject nutriture for copper will also be assessed by measurement of plasma concentrations of copper. Subjects will be monitored for three years for infectious diseases, cancers, and mortality from all causes. Data will be analyzed by a multiple regression approach to analysis of covariance. The study will allow determination of whether the expected beneficial effects of zinc on immunocompetence are due to correction of mild to moderate zinc deficiency and/or to a pharmacologic effect of high doses of zinc, and thus provide data on the mechanisms by which zinc produces its beneficial effects. Assessing a variety of measures of immunocompetence will allow determination of those most favorably affected by zinc administration. Theoretically, both infectious diseases and carcinogenesis could be favorably affected by enhanced cellular immunity. Thus, considerable benefit could be derived from a study of the effects of zinc on cellular immunity in the elderly, a group with a high incidence of both cancers and life-threatening infectious diseases.