Background Zinc deficiency impairs immune function and is common among children in South-East Asia. Objectives The effect of zinc supplementation on immune function in young Laotian children was investigated. Methods Children (n = 512) aged 6–23 mo received daily preventive zinc tablets (PZ; 7 mg Zn/d), daily multiple micronutrient powder (MNP; 10 mg Zn/d, 6 mg Fe/d, plus 13 other micronutrients), therapeutic dispersible zinc tablets only in association with diarrhea episodes (TZ; 20 mg Zn/d for 10 d after an episode), or daily placebo powder (control). These interventions continued for 9 mo. Cytokine production from whole blood cultures, the concentrations of T-cell populations, and a complete blood count with differential leukocyte count were measured at baseline and endline. Endline means were compared via ANCOVA, controlling for the baseline value of the outcome, child age and sex, district, month of enrollment, and baseline zinc status (below, or above or equal to, the median plasma zinc concentration). Results T-cell cytokines (IL-2, IFN-γ, IL-13, IL-17), LPS-stimulated cytokines (IL-1β, IL-6, TNF-α, and IL-10), and T-cell concentrations at endline did not differ between intervention groups, nor was there an interaction with baseline zinc status. However, mean ± SE endline lymphocyte concentrations were significantly lower in the PZ than in the control group (5018 ± 158 compared with 5640 ± 160 cells/μL, P = 0.032). Interactions with baseline zinc status were seen for eosinophils (Pixn = 0.0036), basophils (Pixn = 0.023), and monocytes (P = 0.086) but a significant subgroup difference was seen only for eosinophils, where concentrations were significantly lower in the PZ than in the control group among children with baseline plasma zinc concentrations below the overall median (524 ± 44 compared with 600 ± 41 cells/μL, P = 0.012). Conclusions Zinc supplementation of rural Laotian children had no effect on cytokines or T-cell concentrations, although zinc supplementation affected lymphocyte and eosinophil concentrations. These cell subsets may be useful as indicators of response to zinc supplementation. This trial was registered at clinicaltrials.gov as NCT02428647.
Patients with beta-thalassaemia increase the risk of bacterial infections, particularly Burkholderia pseudomallei (Bp), the causative agent of melioidosis in Thailand. Impaired immune cell functions may be the cause of this susceptibility, but detailed mechanisms have not been defined. In this study, we observed impaired production of IFN-gamma and IL-10 by whole blood from beta-thalassaemia patients upon stimulation with a range of bacteria-derived stimuli. In contrast, IFN-gamma response via TCR and plasma IgG specific for Bp were still intact. Importantly, mRNA expression of heme oxygenase 1 (HO-1), a potential modulator of immune function, was increased in whole blood from beta-thalassaemia patients, either with or without stimulation with Bp in vitro. Induction of HO-1 by hemin or CoPP in vitro reduced production of IFN-gamma and IL-10 from healthy human PBMCs and decreased bacterial clearance activity of whole blood from healthy controls and beta-thalassaemia, while inhibition of HO-1 by SnPP enhanced both functions in healthy controls. These results were confirmed to some extent in purified human monocytes of healthy controls. Our results suggest a mechanism that excess hemin of beta-thalassaemia patients is a significant cause of immune suppression via HO-1 induction and may underlie the susceptibility of these individuals to severe bacterial infection. Thalassaemia, a genetic defect in hemoglobin synthesis, is a public health problem worldwide 1. β-Thalassaemia is a common type of thalassaemia disease which is frequently found in East India, Bangladesh, and Southeast Asia 1. Bacterial infections were reported as causes of death in thalassaemia patients 2. In Thailand, thalassaemia and diabetes mellitus are major risk factors for life-threatening infection by Burkholderia pseudomallei (Bp), so called melioidosis 3. In areas where Bp is endemic, most people who have been exposed are seropositive, and develop pre-existing immunity against this bacteria, with only a minority of otherwise immunocompetent individuals progressing to clinical disease 4. Understanding melioidosis pathogenesis is crucial to improve prevention of disease, particularly in people with underlying conditions 5. Recruitment of immune cells including neutrophils, macrophages, natural killer (NK) cells, NK T cells and T cells occurs at sites of Bp infection 6-8. Bp clearance can be mediated by plasma antibodies which enhance bacterial killing by neutrophils and macrophages 9. Several pro-and anti-inflammatory cytokines are produced in response to bacterial components which modulate immune homeostasis, resulting in potentially protective inflammatory responses 10. Interferon-gamma (IFN-γ) has been reported as a crucial
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