Oral zinc supplementation in Down's syndrome: restoration of thymic endocrine activity and of some immune defects

Abstract

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 pi a sin.i levels of a nonapeptide thymic hormone, i.e. Serum Thymic Factor (STF), high plasma levels of inactive zinc‐unbound STF molten les, 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 immunologicalty 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 utiendance after zinc supplementation wore 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 in 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.

Age‐dependent decreases in mitogen‐stimulation level and RNA content in peripheral blood mononuclear cells of down syndrome patients

“…Our results are concordant also with those of Park et al (27) who reported with trisiated-Thymidine incorporation that PHA-stimulated proliferation of lymphocytes in aged individuals (>30 years old) with DS was significantly lower than that of age-and sex-matched controls. Precocious aging in immune system (28), immuno impairing in general (29)(30)(31), decrease in number of peripheral T-lymphocytes with the phenotype of helper cells (CD4) (32,33) of DS individuals are consistent with our results; since our unpublished results show that PHA stimulates principally and strongly CD4 and CD8 T-lymphocytes. Although the value of RNA contents in nonstimulated (11) and stimulated PBMC as given in this study is higher in infants and children with DS, these subjects suffer nonetheless from immune deficiency.…”

Oral zinc supplementation in Down's syndrome subjects decreased infections and normalized some humoral and cellular immune parameters

“…A precocious deterioration of the thymic dependent branch of the immunity is present in DS subjects. A diminished reactivity to skin tests in vivo (Sutnik et al 1971), a decreased number of circulating T lymphocytes (Franceschi et al 1978;Franceschi et al 1988;Licastro et al 1990b), and an impairment of lymphocyte proliferative capacity after polyclonal activation in vitro (Agarwal ei al. 1970;Raynaud etal.…”

Zinc: dietary intake and impact of supplementation on immune function in elderly

“…Therefore, caution is advised for the management of zinc supplementation with the suggestion to perform the trial for short periods and on alternate cycles only. Following this concept, zinc treatment (even if as zinc sulphate form) at the dose of 15 mg Zn ++ /day for 1 month at alternating cycles in Down's syndrome subjects, in elderly and in old infected patients restores thymic endocrine activity, lymphocyte mitogen proliferative response, CD4(+) cell number, NK cell cytotoxicity, pro-inflammatory cytokine production (Mocchegiani et al 2003;Franceschi et al 1988;Kahmann et al 2006;Kahmann et al 2008) and DNA repair (Chiricolo et al 1993). Clinically, significant reductions of relapsing infections occur in Down's syndrome subjects (Licastro et al 1994), in elderly and in old infected patients (Mocchegiani et al 2003;Prasad et al 2007).…”