Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients

Zinc deficiency is common in adult sickle-cell disease (SCD) patients. We previously demonstrated that zinc supplementation to adult SCD patients decreased the incidences of infections and hospital admissions. We hypothesize that zinc supplementation improves T-helper cell function and decreases vascular endothelial cell activation, oxidative stress, and nuclear factor-kappa B (NF-κB)-DNA binding in mononuclear cells (MNCs) in SCD patients. To test this hypothesis, 36 SCD patients were recruited and randomly divided into 2 groups. One group (n = 18) received 25-mg zinc orally thrice a day for 3 months. The other group (n = 18) received placebo. The results indicate that the zinc-supplemented group had decreased incidence of infections compared with the placebo group. After zinc supplementation, red blood cell, hemoglobin (Hb), hematocrit, (Hct), plasma zinc, and antioxidant power increased; plasma nitrite and nitrate (NOx), lipid peroxidation products, DNA oxidation products, and soluble vascular cell adhesion molecule-1 decreased in the zinc-supplemented group, compared with the placebo group. Zinc-supplemented patients exhibited significant decreases in lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-α) and IL-1β mRNAs, and TNF-induced nuclear factor of κB−DNA binding in MNCs, compared with the placebo group. Ex vivo addition of zinc to MNCs isolated from the placebo subjects decreased TNF-α and IL-1β mRNAs. Zinc supplementation also increased relative levels of IL-2 and IL-2Rα mRNAs in phytohemagglutinin-p−stimulated MNCs. These results suggest that zinc supplementation may be beneficial to SCD patients.

Abbreviations: 8-OHdG, 8-hydroxy-2′-deoxyguanosine, ELISA, enzyme-linked immunosorbent assay, EMSA, electrophoretic mobility shift assay, Hb, hemoglobin, Hct, hematocrit, ICAM-1, intercellular adhesion molecule-1, IFN-γ, interferon-gamma, IL, interleukin, IL-2Rα, IL-2 receptor-alpha, LPS, lipopolysaccharide, MDA + HAE, malondialdehyde + hydroxyalkenals, MNC, mononuclear cell, NADPH, nicotinamide adenine dinucleotide phosphate-oxidase, NF-κB, nuclear factor-kappa B, NOx, nitrite and nitrate, PHA, phytohemagglutinin-p, RBC, red blood cell, ROS, reactive oxygen species, RT-PCR, reverse transcription-polymerase chain reaction, SCD, sickle cell disease, TNF-α, tumor necrosis factor-alpha, URI, upper respiratory infection, VCAM-1, vascular cell adhesion molecule-1