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

European Journal of Clinical Nutrition volume 58, pages 1498–1504 (2004)Cite this article

Abstract

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).

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Acknowledgements

We would like to thank the mothers and the infants who participated in this study, and we are grateful for the enthusiastic help we received from Dr Hendra and his staff and from all the health volunteers from Situ Udik and Situ Ilir. Furthermore, we like to thank all the members of our field team, and the staff from the laboratories in Bogor, Nijmegen and Wageningen, for their untiring efforts and warm cooperation. Especially, we would like to thank Dr R Hermsen for the analysis of IL-12p70.

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Authors and Affiliations

  1. Department of Internal Medicine, University Hospital Nijmegen, The Netherlands

    F T Wieringa, M A Dijkhuizen, J van der Ven-Jongekrijg & J W M van der Meer

  2. Division of Human Nutrition and Epidemiology, Wageningen Agricultural University, The Netherlands

    F T Wieringa, M A Dijkhuizen & C E West

  3. Nutrition Research and Development Centre, Bogor, Indonesia

    F T Wieringa, M A Dijkhuizen &  Muhilal

  4. Department of Gastroenterology, University Medical Centre Nijmegen, The Netherlands

    C E West

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  1. F T Wieringa
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  2. M A Dijkhuizen
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  3. C E West
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  4. J van der Ven-Jongekrijg
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  5. Muhilal
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  6. J W M van der Meer
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Contributions

Guarantor: JWM vd Meer.

Contributors: FTW and MAD were involved in the design, implementation, analysis of the study, and drafting of the manuscript. CEW as involved with the design of the study and drafting of the manuscript, JvdV-J was involved with the design and laboratory analysis of the study, Muhilal was involved in the design and implementation of the study, and JWM vd M was involved in design and analysis of the study. All authors contributed to the final version of the manuscript.

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Correspondence to F T Wieringa.

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Wieringa, F., Dijkhuizen, M., West, C. et al. Reduced production of immunoregulatory cytokines in vitamin A- and zinc-deficient Indonesian infants. Eur J Clin Nutr 58, 1498–1504 (2004). https://doi.org/10.1038/sj.ejcn.1601998

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