Differential response of interleukin-2 production to chronic copper supplementation in healthy humans

Copper (Cu) is an essential trace element for many biological processes including maintenance of both innate and acquired branches of immunity.

To measure the effect of copper supplementation on IL-2 and TNF-alpha production in subjects with lower and higher ceuloplasmin (Cp) values within normal range.

Healthy adults (17 men and 16 women) with normal-low (low Cp) and normal-high Cp (high Cp) values were supplemented with 10 mg Cu/day (as CuSO(4)) during 2 months.

Before and after supplementation blood mononuclear cells were incubated in the absence or presence of phytohaemagglutinin or lipopolysaccharide for induction of IL-2 and TNF-alpha, respectively. The secretion of cytokines was measured by ELISA. Cu supplementation did not modify classical biochemical markers of Cu status.

After supplementation, a significant increase in IL-2 production was found only in subjects with normal-low plasma Cp. Before and after Cu supplementation geometric mean and range +/- 1 SEM values were 1,566 (1,287-1,905) and 2,514 (2,159-2,927) pg/mL, respectively (two-way ANOVA for repeated measures: Cp level p < 0.001; time = NS; interaction Cp level and time p < 0.05). We did not observe changes in TNF-alpha production after Cu supplementation.

Cu supplementation increased secretion of IL-2 and not TNF-alpha, which suggests an activation of proliferative but not inflammatory cytokines. These results support hypothesis that IL-2 may be a good indicator to identify a subgroup of individuals (polymorphism) who differs in Cu metabolism.