The effect of at-birth vitamin A supplementation on differential leucocyte counts and in vitro cytokine production: an immunological study nested within a randomised trial in Guinea-Bissau

• Published in: British journal of nutrition 2013-02, Vol.109 (3), p.467-477
• Main Authors: Jørgensen, Mathias J., Fisker, Ane B., Sartono, Erliyani, Andersen, Andreas, Erikstrup, Christian, Lisse, Ida M., Yazdanbakhsh, Maria, Aaby, Peter, Benn, Christine S.
• Format: Article
• Language: English
• Subjects: BCG Vaccine - immunology; Biological and medical sciences; Cells, Cultured; Child Development; Cytokines; Cytokines - metabolism; Dietary Supplements; Diterpenes; Double-Blind Method; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Guinea-Bissau; Health promotion; Humans; Immune system; Immunity, Cellular; Immunity, Innate; Immunomodulation; Infant, Newborn; Leukocyte Count; Leukocytes; Leukocytes - cytology; Leukocytes - immunology; Leukocytes - metabolism; Male; Monocytes - cytology; Monocytes - immunology; Monocytes - metabolism; Mortality; Newborn babies; Nutritional Immunology; Retinyl Esters; Sex Characteristics; Tuberculosis - immunology; Tuberculosis - prevention & control; Vaccines; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin A; Vitamin A - administration & dosage; Vitamin A - analogs & derivatives; Vitamin A - therapeutic use
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114512001304

Vitamin A supplementation (VAS) at birth was not associated with improved survival in a randomised, placebo-controlled trial in Guinea-Bissau. However, a negative sex-differential effect, which became evident after diphtheria–tetanus–pertussis (DTP) vaccination, was noted; among girls who had received DTP, VAS at birth was associated with two-fold higher mortality than placebo. The objective of the present study was to investigate the immunological effects of VAS at birth within a subgroup of participants in the randomised trial. Guided by the mortality results, we further explored whether VAS had a differential effect according to sex and DTP status. At 6 weeks after randomisation and supplementation, we measured differential leucocyte counts and TNF-α, interferon-γ, IL-10, IL-13 and IL-5 production in a whole-blood culture assay. A total of 471 children were included. VAS compared with placebo at birth was associated with a higher proportion of monocytes (relative risk ratio 1·26, 95 % CI 1·07, 1·49, P= 0·04), while spontaneous TNF-α production was lower in the VAS group (geometric mean ratio 0·54, 95 % CI, 0·37, 0·78, P= 0·001). Stratified analysis showed that VAS was associated with lower TNF-α and IL-10 production for girls without DTP and boys with DTP, resulting in significant three-way interactions between VAS, sex and DTP vaccination status (P= 0·03 and P= 0·04, respectively) for spontaneous TNF-α and IL-10 production. The results substantiate the potential role of VAS as an immunomodulatory intervention, which has different effects depending on concomitant health interventions and the sex of the recipient.