The overall focus of this laboratory is to contribute to the understanding of trace elements in human health and disease. Considerable attention has been directed towards determining the metabolic and immunologic consequences of iron deficiency. The role of iron in the immune response and in infection has been enigmatic for some time, with both detrimental and protective effects of iron deficiency observed in field studies of malnourished populations. We have systematically studied the immune response system in experimental models to determine which components are affected by iron deficiency and what mechanisms are responsible. Synthesis of antibodies and some of the cytokines such as interleukin 1 and 2 have been found to be impaired by iron deficiency. Progression through the cell cycle is distorted in iron deficiency and abnormalities in the normal distribution of lymphocyte subsets contributes to the impaired immune responsiveness in iron deficiency.

Various components of cell- mediated immunity, including phagocytosis and cytotoxicity by natural killer cells and macrophages are part of the host’s immunosurveillance against tumor cells. We have begun to study the effect of iron status on carcinogenesis. In a rodent model of breast cancer we have found that iron deficiency is protective against tumors induced by the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). As shown in the figure, iron-deficient rats had a later onset and lower incidence of tumors that did rats fed adequate iron (control), rats initially made iron deficient and then repleted with iron after DMBA treatment (repleted), or rats fed an iron-adequate diet in the lower amounts eaten by the iron- deficient group (pair-fed). Present research is directed towards identifying the mechanism(s) responsible for this effect.

In addition to the work utilizing animal models, human subjects have been studied. Earlier, we established that iron status can be compromised by a moderate program of aerobic exercise. Recently, iron status and immunocompetence was studied in infants breast fed or fed formula containing two different levels of iron. Adequate iron status and immunocompetence was achieved with all feeding modalities, and no differences in illness incidence was observed during the infants' first year. Present human studies in collaboration with others focus on immunity and nutritional status in the elderly as related to mental health parameters.

Leiter, L.M. and A.R. Sherman (1994) Differential effects of iron status on lymphocyte subsets in lupus and non-lupus strains of mice. Nutrition Research 14:1407- 1422.

Leiter, L.M. and A.R. Sherman (1995) Iron status alters murine systemic lupus erythematosus. Journal of Nutrition 125:474-484. Hrabinski, D., J.L. Hertz, C. Tantillo, V. Berger, and A.R. Sherman (1995) Iron repletion attenuates the protective effects of iron deficiency in DMBA-induced mammary tumors in rats. Nutrition and Cancer 24:133-142.

Monteleone, C.A. and A.R. Sherman (1997) Nutrition and asthma. Archives in Internal Medicine 157:23-34.