Diets specifically deficient in selenium (Se) and/or vitamin E or adequate in both nutrients were fed to chicks from the time of hatching. Lymphoid organs (bursa, thymus, and in some instances, spleen) were collected from chicks 7-35 days of age. Growth of the chicks fed these diets was monitored over the experimental period as was lymphoid organ growth. The development of the primary lymphoid organs was further assessed by histological techniques and the organ contents of vitamin E (a-tocopherol) and Se were determined. Specific deficiencies of either Se or vitamin E were found to significantly impair bursal growth as did a combined deficiency. Thymic growth was impaired only by the combined deficiency diet. Severe histopathological changes in the bursa resulted from the combined deficiency and these were detectable by 10-14 days after hatching. These changes were characterized by a gradual degeneration of the epithelium and an accompanying depletion of lymphocytes. Similar changes, although slower to develop and less severe, were observed in the thymus as a result of the combined deficiency. When both serum and tissue levels of vitamin E and Se were monitored, it was observed that these were rapidly and independently depleted by the specific deficiency diets. These data suggest that the primary lymphoid organs are major targets of Se and vitamin E dietary deficiencies and provide a possible mechanism by which immune function may be impaired.

Selenium is a trace element essential for the health and development of the growing infant. It is a necessary component of proteins and enzymes required for a variety of functions, including antioxidant defense, modulation of the inflammatory response, and production of thyroid hormones. In breast-fed infants, selenium stores depend on the selenium content of the mother's diet. In formula-fed infants, selenium levels are correlated to the residual selenium stores accumulated in utero and the level and type of selenium fortification used in the formula. Today, the United States Food and Drug Administration (FDA) recommends that infant formulas contain selenium at levels between 2.0 and 7.0 μg per 100 kcal. While the US FDA does not recommend a particular selenium form for fortification, evidence indicates that organically bound selenium forms (e.g., selenomethionine and selenium-enriched yeast) are better absorbed and retained than inorganic forms (e.g., selenite and selenate). Preliminary data from studies in adults do suggest that fortification with standardized selenium-enriched yeast may offer benefits compared to fortification with other organically bound selenium forms. However, because most studies evaluating the impact of selenium fortification of infant formula have assessed inorganic selenium supplements, additional research into the bioavailability and outcomes associated with the use of selenium-enriched yeast in infants is needed.

The activity of selenium-dependent glutathione peroxidase (SeGSH-Px) in the pancreas was found to decline in response to Se depletion in the chick at approximately the same time as the appearance of histopathological changes in the acinar cells of the pancreas, indicative of the onset of nutritional pancreatic atrophy. Oral administration of 10 micrograms of Se as Na2SeO3 to Se-deficient chicks increased SeGSH-Px activity in liver and plasma within 12 hours but not in pancreas until 36 hours. Histological signs of regeneration were not observed within 48 hours of Se repletion; however, acinar nuclei were significantly larger within 12 hours of Se repletion. The apparent rates of synthesis of DNA, RNA, and protein in liver, and of DNA in pancreas, were not affected by Se deficiency. The apparent rates of synthesis of pancreatic RNA and protein were depressed in Se-deficient chicks and were increased within 24 and 36 hours, respectively, upon Se repletion. Electron microscopic observation of pancreatic acinar cells from Se-deficient chicks revealed disruption of inner and outer mitochondrial membranes. However, no impairment was noted in rate of oxygen uptake, respiratory control index, or ADP:oxygen ratio of pancreatic mitochondria due to Se deficiency. The mitochondrial protein yield of the Se-deficient chick pancreases was 27% less than that of Se-adequate chicks. These data suggest that a decreased number of functional acinar mitochondria may result in nutritional pancreatic atrophy in the Se-deficient chick.

Studies were conducted to determine the relationship between dietary vitamin E (VE) and the development of nutritional pancreatic atrophy (NPA) in selenium (Se)-deficient chicks. Selenium- and VE-depleted chicks reared on a low Se, amino acid-based diet containing 100 IU VE (as all-rac-alpha-tocopheryl acetate) per kilogram were found to have exceedingly low pancreatic activities of Se-dependent glutathione peroxidase (SeGSHpx) at 8 d of age. Supplementation of the purified diet with 500 or 1,000 IU VE/kg prevented both NPA and the associated growth depression. Use of graded dietary VE levels showed that addition of at least 300 IU/kg was required to overcome the growth depression associated with severe Se deficiency. Although tissue alpha-tocopherol concentrations increased linearly with increasing dietary levels of VE, the response in pancreas was less than (about one-half of) those in liver and heart and, unlike the response in heart, was not affected by dietary Se level. That protection against NPA involved the antioxidant action of VE was suggested by results showing that NPA is promoted by high dietary levels of linoleic acid, that high VE levels correct membrane unsaturated fatty acid losses due to Se deficiency and that NPA is prevented by high levels of other antioxidants. It is suggested that the normally low activities of SeGSHpx and concentrations of alpha-tocopherol in the pancreas may predispose that organ to lesions due to oxidative stress under conditions of severe nutritional Se deficiency that results in further depletion of SeGSHpx. This situation may be overcome by feeding VE at 15-20-fold excesses over the levels normally regarded as nutritionally required.