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The effect of 4 months of oral zinc supplementation on immune functions in non-institutionalized young female and male Down's syndrome (DS) subjects was studied. Along with plasma levels of zinc, the immune parameters, measured before and after zinc treatment, were plasma levels of thymulin, the percentage and the absolute number of circulating white blood cells, total lymphocytes, lymphocyte subpopulations, the mitogen-induced lymphocyte proliferation, the production of interleukin-2, and the activity of stimulated granulocytes. Some immune parameters were significantly influenced by zinc treatment. In particular, a normalization of thymulin and zinc plasma levels were found in these subjects after zinc supplementation. At the end of the clinical trial, in vitro lymphocyte proliferation and polymorphonuclear activity also increased and reached normal values. Zinc administration exerted a positive clinical effect in these children, since a reduced incidence of infections was found.

Oral zinc supplementation is able to correct zinc deficiency and some immune defects present in Down's syndrome (DS), while other beneficial effects can be predicted because of the broad spectrum of biochemical pathways and the great variety of enzymes which depend on zinc bio-availability. To test if the maintenance of DNA integrity is also affected by zinc supplementation, DNA damage and repair after gamma-radiation was studied by alkaline elution assay in phytohemagglutinin-stimulated lymphocytes from Down's syndrome children before and after an oral zinc supplementation given for 4 months to correct their immune defects. In comparison with lymphocytes from normal children the DNA damage induction after ionizing radiation in DS lymphocytes both before and after zinc supplementation was normal. On the other hand, the rate of DNA repair in DS was highly and significantly accelerated before zinc treatment. After supplementation with zinc sulfate, the DNA repair rate was consistently slowed down becoming similar to that of control subjects. This is the first demonstration that a nutritional intervention in humans is apparently able to modify the biochemical steps which control the rate of DNA repair.

Metabolic activation of peripheral blood leukocytes (chemiluminescence) from 27 children with Down syndrome (DS) and 23 age and sex-matched control children after phagocytic stimulation by opsonized zymosan particles was investigated through a chemiluminescence assay. Using autologous plasma or serum as opsonizing media, phagocytic activity of circulating leukocytes was significantly decreased in DS subjects. A further decrease of phagocytic activity was found in neutrophils from DS children, when normal heterologous plasma or sera were used. On the other hand, sera or plasma from DS subjects significantly increased phagocytic activation of leukocytes from normal donors. In DS subjects opsonizing agents such as serum immunoglobulins and complement fractions were in the normal ranges of concentration. Thus, the impaired chemiluminescence of neutrophils was mainly due to a metabolic impairment at the cellular level. A decreased production of radicals derived from the oxygen metabolism in neutrophils may be an important step of immune derangement leading to the increased incidence of infectious diseases frequently associated with DS.

The effect of different concentrations of LiCl or KCl (0.6-20 meq/liter) on PHA-stimulated lymphocytes from young, old, and Down's syndrome subjects was studied. LiCl showed a dramatic enhancing effect on [3H]thymidine incorporation induced by a suboptimal dose of PHA in old subjects and Down's syndrome patients. An increase of [3H]thymidine incorporation in human lymphocytes stimulated by a suboptimal dose of PHA was also observed with KCl. This effect was higher in old subjects than that observed in young and Down's subjects. LiCl and KCl can modulate and partially restore the derangement in early events of mitogen stimulation which seems to be present in lymphocytes from both old and Down's syndrome subjects.

The redistribution with the time of concanavalin A (Con A) receptors at one pole of the cell after addition of FITC-Con A - so-called capping - in the peripheral blood lymphocytes from 13 aged subjects (mean: 84 +/- 1 years old), and of 16 noninstitutionalized patients affected by a syndrome of precocious aging, such as Down's syndrome (mean: 17 +/- 2 years old), was studied and compared with a group of 15 normal young people (mean: 23 +/- 2 years old). An opposite alteration in the percentage of capped cells, i.e. a decrease in aged subjects and an increase in Down's syndrome patients, was observed. A derangement of lymphocyte membrane fluidity appears to be present in both groups even if the underlying biochemical defect may be different. However, a similar alteration of the kinetics of the phenomenon was present either in aged or in Down's syndrome subjects. Both groups did not show any significant increase with time of the percentage of capped cells, suggesting that they were lacking a lymphocyte subpopulation(s) which start capping later.

Eighteen non-institutionalized Down's syndrome (DS) children (mean age: 7.0 +/- 10/12 years) with a history of respiratory tract, auditory and skin infections, low plasma levels of a nonapeptide thymic hormone, i.e. Serum Thymic Factor (STF), high plasma levels of inactive zinc-unbound STF molecules, and reduced absolute number of circulating T-lymphocytes, were given an oral non-pharmacological supplementation of zinc sulphate (1 mg Zn++/kg body weight/day for 2 months; two cycles, 10 months apart) and monitored immunologically before and after each cycle. A dramatic increase of plasma STF level and concomitantly an almost complete disappearance of inactive STF molecules was observed after each cycle. The absolute number of circulating T-lymphocytes was significantly increased by zinc treatment. The marginal zinc deficiency was also corrected without any appreciable influence on copper plasma levels. A reduction of recurrent infections and an improvement in school attendance after zinc supplementation were recorded. These beneficial effects of zinc supplementation were also noted in those DS children who did not show an apparent zinc deficiency, as assessed by measuring zinc plasma level. The reduced number of circulating B lymphocytes and the impaired lymphocyte responsiveness to phytohaemagglutinin and concanavalin A were not restored. On the whole, these findings suggest that there exists a defect in the bio-availability and/or in the utilization of zinc in DS. This alteration, of unknown origin, can be underestimated on the simple basis of the zinc plasma level and can be corrected with moderate nutritional zinc supplementation.