F.T. Wieringa

Reduced production of immunoregulatory cytokines in vitamin A- and zinc-deficient Indonesian infants

Objective: To determine effects of vitamin A, zinc and iron deficiency in Indonesian infants on the ability to produce immunoregulatory cytokines.Design, setting and subjects: Immunological asssessment was done in 59 infants participating in a cross-sectional nutritional survey in rural West Java, Indonesia. Production of T-helper cell type-1 (Th1, cell-mediated) cytokines interferon-γ (IFN-γ), interleukin-12 (IL-12), interleukin-18 (IL-18) and T-helper cell type-2 (Th2, humoral) cytokine interleukin-6 (IL-6) were measured after stimulation with lipopolysaccharide and phytohemagglutinin in an ex vivo whole blood culture system. Circulating neopterin concentrations were determined as an indicator of in vivo macrophage activity.Results: Of the infants, 48% were vitamin A deficient, 44% were anemic (with 17% having iron deficiency anemia), and 17% were zinc deficient. Vitamin-A deficient infants had significantly reduced ex vivo production of IFN-γ, but also significantly higher circulating neopterin concentrations. Production of IFN-γ and IL-12 were strongly correlated, IFN-γ and IL-18 production were not. Zinc deficiency was accompanied by significantly reduced white blood cell counts and reduced ex vivo production of IL-6. Iron status was not related to cytokine production.Conclusions: This study shows that in vitamin A deficiency there is Th1 dominance in a steady state, combined however with impairment of the Th1 response after stimulation, whereas in zinc deficiency, there is a decreased Th2 response. Overall, vitamin A deficiency and zinc deficiency have marked albeit different effects on the immunocompetence of infants, affecting both cell-mediated and humoral components of the immune system.Sponsorship: Netherlands Foundation for the Advancement of Tropical Research (WOTRO), and Ter Meulen Fund (Royal Netherlands Academy of Arts and Sciences).

Maternal micronutrient supplementation with zinc and β-carotene affects morbidity and immune function of infants during the first 6 months of life

Background/Objectives:Micronutrient deficiencies are prevalent worldwide, and a major cause of infant death. Supplementation with multiple micronutrients during pregnancy might improve micronutrient status of the newborn, thereby reducing morbidity and death. Moreover, maternal supplementation might affect the newborns immune development. Therefore, this study investigated the effects of maternal zinc and β-carotene supplementation on the infants morbidity and immune function during the first 6 months of life.Subjects/Methods:Mothers were supplemented during pregnancy with β-carotene and/or zinc, in addition to iron and folic acid, in a randomized, double-blind controlled trial. Newborn infants (n=136) were followed up for 6 months.Results:Infants born from mothers receiving zinc during pregnancy had significantly fewer episodes of diarrhoea than infants born from mothers not receiving zinc (0.2 and 0.4, respectively), but more episodes of cough (1.3 and 0.9 respectively) during the first 6 months. Maternal β-carotene supplementation had no effect on infants’ morbidity. Cytokine production in the newborns was affected by maternal zinc and β-carotene supplementation, with zinc supplementation giving higher interleukin-6 production (16% higher), and β-carotene supplementation leading to lower interferon-γ production (36% lower).Conclusions:This study shows that maternal supplementation with zinc and β-carotene affected the newborns immune development in specific ways, but only maternal zinc supplementation significantly affected morbidity in the infants. Addition of zinc to routine iron and folic acid supplements for pregnant women could be an effective way to reduce diarrhoeal disease during the first 6 months of life, albeit at the expense of more episodes of cough.

Micronutrient Deficiency and Supplementation in Indonesian Infants

Health of infants in developing countries is constantly challenged by pathogens. Unfortunately, the immune system of newborn infants is immature, developing during the first year of life to attain adequate immunocompetence at about one year of age. During the first few months of life, maternal antibodies (especially IgG) acquired in utero circulate and protect the newborn. In addition, via breast milk, the infant acquires considerable amounts of immunoglobulins (mostly sIgA) and possibly other humoral and cellular components of the mother’s immune defence. The protective effect of sIgA in breast milk is restricted to the gut. The precise role of the other immunomodulatory components of breast milk, remains unclear.