M E Gershwin

Influence of Dietary Aluminum on Cytokine Production by Mitogen-Stimulated Spleen Cells from Swiss Webster Mice

Swiss Webster mice were exposed to excess dietary aluminum (Al) (1000 micrograms Al/g diet, Al as Al lactate) from conception to 6 months of age. Splenic lymphocytes (10(6) per culture) were incubated for 24 hrs with concanavalin A (5 micrograms/ml). Concentrations of interleukin-2, interferon-gamma and tumor necrosis factor-alpha, as measured in supernatants via ELISA with monoclonal antibodies, were depressed in spleen cells from aluminum treated mice relative to controls. Experiments using the fluorescence activated cell sorter demonstrated a shift in T-cell populations from treated mice with a deficiency of CD4+ cells. These findings suggest a deficit in immune effector cell function after long term in vivo aluminum exposure.

Influence of Marginal Maternal Zinc Deficiency on Pregnancy Outcome and Infant Zinc Status in Rhesus Monkeys

ABSTRACT: To investigate the effects of marginal zinc deficiency on early development, rhesus monkeys were fed a diet marginally deficient in zinc (M; 4 μg/g) throughout pregnancy and during the first month of lactation. Despite the low concentration of zinc in the diet, M dams did not develop overt signs of zinc deficiency. However, compared to control dams fed diets adequate in zinc (C; 100 μg Zn/g), M dams showed a low response to the mitogens concanavalin A and phytohemagglutinin. Pregnancy outcome was similar in the two groups and all of the neonates were judged to be healthy at delivery. From birth until d 30 of age, the infants were closely monitored for signs of zinc deficiency, and at d 30, they were killed and tissues were removed and analyzed for a number of parameters reported to be affected by zinc status. At birth, M infants had low plasma zinc concentrations compared to controls; however, this difference was not observed at d 30. D 30 M infants showed a normal response to the mitogens concanavalin A and phytohemagglutinin, but showed a low response to pokeweed mitogen. Tissue (liver, brain, spleen, kidney, and heart) trace element concentrations were similar in the two groups of infants, as were liver metallothionein concentrations and 65Zn uptake/retention by isolated hepatocytes. Infant wt gain was inversely correlated with plasma zinc, liver zinc, and liver metallothionein concentrations in both the M and C groups. These results demonstrate that feeding a diet containing 4 μg zinc/g to rhesus monkeys during pregnancy and lactation does not result in marked signs of zinc deficiency, although subtle signs occur in both the mother and infant. The data also support the concept that infant growth is associated with a depletion of tissue zinc stores.

Effect of the Severity of Maternal Zinc Deficiency on Pregnancy Outcome and Infant Zinc Status in Rhesus Monkeys

ABSTRACT: To investigate the effects of the severity of maternal zinc deficiency on early development, rhesus monkeys were fed diets that were either moderately zinc-deficient (MZD) (2 μg Zn/g) or marginal in zinc (M) (4 μg Zn/g throughout pregnancy and lactation. Dams in the MZD group developed overt signs of zinc deficiency. Compared with control dams fed diets adequate in zinc (C) (50 or 100 μg Zn/g), both M and MZD dams showed low mitogen response. Pregnancy outcome was similar in all groups, and infants were considered healthy at delivery. From birth until d 30, infants were closely monitored for signs of zinc deficiency. On d 30, infants were killed and tissues were analyzed for several parameters reported to be affected by zinc status. MZD infants tended to have lower plasma zinc concentrations than C infants, although the difference was only significant at d 14. M infants tended to have lower plasma zinc concentrations than C infants. Mitogen response was lower in MZD and M infants than in C infants. However, mitogen responses were similar in MZD and M infants. Liver zinc concentrations were similar among the three groups of infants; however, zinc and metallothionein concentrations in (10 000 × g) liver supernatant fractions were lower in the MZD and M groups than in the C group. 65Zn absorption/retention was higher in MZD and M mothers and infants than in C mothers and infants; there were no marked differences between MZD and M mothers or infants. In contrast to whole-body absorption, 65Zn uptake/retention by isolated hepatocytes was similar among the three infant groups. Plasma metallothionein concentrations were higher in the MZD mothers during the 1st, 2nd, and 3rd trimester than in the M or C mothers and higher than C mothers on d 30 postpartum; plasma metallothionein concentrations were similar among the three groups of infants. These results demonstrate that feeding a diet containing 2 μg Zn/g to rhesus monkeys during pregnancy and lactation results in marked signs of zinc deficiency, whereas feeding a diet containing 4 μg Zn/g results in only subtle signs.

Effect of infant formula zinc and iron level on zinc absorption, zinc status, and immune function in infant rhesus monkeys.

To evaluate the effects of marginal zinc (Zn) deficiency on Zn absorption and metabolism, three groups of infant rhesus monkeys (n = 4/group) were fed from birth to 5 months of age either a regular infant formula (5 mg Zn/L) or a low-Zn formula (1 mg Zn/L). Since iron (Fe) intake may affect Zn absorption, the low-Zn formula was given without (1 mg Fe/L) or with Fe fortification (12 mg/L). At monthly intervals, Zn absorption and retention were assessed by gavage feeding with 65Zn and whole-body counting immediately after and on days 4, 7, and 11 after intubation. Blood samples were drawn before dosing for analyses of various potential markers of Zn status. Infants fed low-Zn formula had lower weight gain than controls; however, length growth was similar in all groups. 65Zn retention was considerably higher in both groups fed low-Zn formula (40%) than in the control group (20%), whereas plasma Zn levels were normal in all infants. Plasma metallothionein levels were generally very low and detectable in only 5 samples of 48; however, 4 of these were found in control infants. Neutrophil chemotaxis assessed at the end of the study was impaired in low-Zn infants compared to controls. In addition, low-Zn infants had increased levels of interleukin-2 at the end of the study. No differences were seen between the groups in hemoglobin levels, total white blood cells/absolute neutrophil counts, or plasma activities of 5-nucleotidase or angiotensin converting enzyme. In conclusion, marginal Zn intake in infant rhesus monkeys resulted in increased Zn retention, which was not enough to completely compensate for the lower Zn intake. The higher level of iron fortification studied did not affect Zn retention significantly.