The influence of Fe status on cell-mediated immunity was studied in weanling mice fed on Fe-deficient (7 mg Fe/kg), Fe-sufficient (120 mg Fe/kg) and high-Fe (3000 or 5000 mg Fe/kg) diets for 7 weeks. The contact sensitivity (CS) response to dinitrofluorobenzene (DNFB), the in vivo delayed-type hypersensitivity (DTH) response to sheep erythrocytes (SRBC) and the ability of primed spleen cells to transfer DTH response to naive normal mice were suppressed in mice consuming the Fe-deficient diet. High-Fe diets (3000 or 5000 mg Fe/kg) selectively suppressed the CS response to DNFB, but the DTH response to SRBC or the transfer of DTH response by primed spleen cells to naive normal mice remained normal. Spleen cell functions associated with the expression of class II major histocompatibility (MHC) surface antigens, concanavalin A-induced interleukin-2 (IL-2) secretion or the antigen-presenting cell (APC) ability to stimulate antigen-dependent proliferation of an SRBC-specific helper T-lymphocyte clone were not altered by Fe status. However, consistent with the suppressed DTH response in the Fe- deficient mice was the suppressed concanavalin A-induced T-lymphocyte blastogenesis and the interferon-γ (INF-γ) production by spleen cells from mice fed on the Fe-deficient diet. Spleen cells from mice fed on excess levels of Fe in the diet secreted less INF-γ than the control mice, although T- lymphocyte proliferation remained unaffected. Suppression of the cellular immune response associated with Fe deficiency may be related in part to impaired T-lymphocyte proliferation and INF-γ secretion rather than to deficits in IL-2 secretion or APC function.

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This study examined the effect of excess dietary iron on liver function, iron and vitamin E status and the protective activity of vitamin E. Consumption of excess dietary iron (3000, 5000, 8000 mg iron/kg/diet) compared with consumption of the control diet (120 mg iron/kg diet) by weanling male CD-1 mice for 7 wk resulted in accumulation of iron in liver, increased relative liver weights and a reduction in hepatic vitamin E stores. The concentration of vitamin E in the liver was negatively correlated with dietary iron concentration (r = 0.998). Weekly administration of vitamin E (20 mg/kg, subcutaneously) prevented iron-induced liver damage without altering hepatic iron stores. Pretreatment of adult male CD-1 mice with a single subcutaneous dose of vitamin E (20 mg/kg body wt) 24 h prior to a lethal dose of iron (60 mg/kg, intraperitoneally) resulted in 100% protection. A similar dose of vitamin E given 5, 30 or 60 min (intravenously) after iron intoxication enhanced survival to 90, 70 and 80%, respectively, compared with the untreated control group. Vitamin E treatment 30 min after iron intoxication reduced mortality by 75% compared with intravenous treatment with 10 mg/kg of deferoxamine (Desferal). Data in this study indicate that vitamin E may be a useful antidote for iron toxicoses and that iron-induced depletion of vitamin E may play a role in the pathogenesis of iron toxicity.

Among environmental contaminants recognized for their toxicity and global distribution, heavy metals are elements known to exert serious ecological consequences. Published experiments on the immunotoxic effects of metals such as methylmercury (MeHg), cadmium (Cd), and lead (Pb) were often conducted at concentrations higher than those present in the environment or those in human blood. In the present study the in vitro effects on human blood of environmentally relevant concentrations of MeHg (33-200 mug/L), Cd (3.1-16 mug/L), and Pb (75-207 mug/L) were assessed individually and in mixtures on the viability and immune competence of peripheral blood leukocytes (PBLs). At MeHg concentrations of 120 and 200 mug/L both lymphocyte proliferation, as measured by [(3)H]thymidine incorporation, and natural killer (NK) cytotoxity activity, as determined by dioctadecyloacarbocyanine, were suppressed. Our results showed an increase of intracellular thiols in lymphocytes and in monocytes at all the concentrations of metals tested. A decrease in the level of metallothionein (MT) was seen in monocytes in presence of Hg at concentration of 120 mug/L and higher. For lymphocytes, a significant increase of MT in groups containing the lower concentrations of Cd, and Hg was noted. In summary, it appears that Hg represents the most toxic metal at environmentally relevant concentrations on human peripheral mononuclear cells. The effects of Hg exposure were greater on lymphocytes and NK cells than on monocytes.

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