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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

  • Mathias J. Jørgensen (a1), Ane B. Fisker (a2), Erliyani Sartono (a3), Andreas Andersen (a1) (a2), Christian Erikstrup (a4), Ida M. Lisse (a4), Maria Yazdanbakhsh (a3), Peter Aaby (a1) (a2) and Christine S. Benn (a1) (a2)...

Abstract

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.

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Corresponding author

*Corresponding author: M. J. Jørgensen, E-mail: mjj@ssi.dk

References

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1Stephensen, CB (2001) Vitamin A, infection, and immune function. Annu Rev Nutr 21, 167192.
2Benn, CS, Diness, BR, Roth, A, et al. (2008) Effect of 50,000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial. BMJ 336, 14161420.
3Humphrey, JH, Agoestina, T, Wu, L, et al. (1996) Impact of neonatal vitamin A supplementation on infant morbidity and mortality. J Pediatr 128, 489496.
4Rahmathullah, L, Tielsch, JM, Thulasiraj, RD, et al. (2003) Impact of supplementing newborn infants with vitamin A on early infant mortality: community based randomised trial in southern India. BMJ 327, 254.
5Benn, CS, Rodrigues, A, Yazdanbakhsh, M, et al. (2009) The effect of high-dose vitamin A supplementation administered with BCG vaccine at birth may be modified by subsequent DTP vaccination. Vaccine 27, 28912898.
6Benn, CS, Fisker, AB, Napirna, BM, et al. (2010) Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial. BMJ 340, c1101.
7Fisker, AB, Lisse, IM, Aaby, P, et al. (2007) Effect of vitamin A supplementation with BCG vaccine at birth on vitamin A status at 6 wk and 4 mo of age. Am J Clin Nutr 86, 10321039.
8da Silva, ZJ, Oliveira, I, Andersen, A, et al. (2008) Changes in prevalence and incidence of HIV-1, HIV-2 and dual infections in urban areas of Bissau, Guinea-Bissau: is HIV-2 disappearing? AIDS 22, 11951202.
9WHO (2010) WHO Recommendations for Routine Immunization – Summary Tables. http://www.who.int/entity/immunization/policy/Immunization_routine_table2.pdf .
10Diness, BR, Fisker, AB, Roth, A, et al. (2007) Effect of high-dose vitamin A supplementation on the immune response to Bacille Calmette-Guerin vaccine. Am J Clin Nutr 86, 11521159.
11Erhardt, JG, Estes, JE, Pfeiffer, CM, et al. (2004) Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique. J Nutr 134, 31273132.
12Agresti, A (2002) Categorical Data Analysis, 2nd ed.New York: Wiley-Interscience.
13Greene, WH (2007) Econometric Analysis, 6th ed.Upper Saddle River, NJ: Pearson/Prentice Hall.
14Uh, HW, Hartgers, FC, Yazdanbakhsh, M, et al. (2008) Evaluation of regression methods when immunological measurements are constrained by detection limits. BMC Immunol 9, 59.
15Barros, AJ & Hirakata, VN (2003) Alternatives for logistic regression in cross-sectional studies: an empirical comparison of models that directly estimate the prevalence ratio. BMC Med Res Methodol 3, 21.
16Wang, X, Allen, C & Ballow, M (2007) Retinoic acid enhances the production of IL-10 while reducing the synthesis of IL-12 and TNF-alpha from LPS-stimulated monocytes/macrophages. J Clin Immunol 27, 193200.
17Mehta, K, McQueen, T, Tucker, S, et al. (1994) Inhibition by all-trans-retinoic acid of tumor necrosis factor and nitric oxide production by peritoneal macrophages. J Leukoc Biol 55, 336342.
18DeCicco, KL, Youngdahl, JD & Ross, AC (2001) All-trans-retinoic acid and polyriboinosinic: polyribocytidylic acid in combination potentiate specific antibody production and cell-mediated immunity. Immunology 104, 341348.
19Cox, SE, Arthur, P, Kirkwood, BR, et al. (2006) Vitamin A supplementation increases ratios of proinflammatory to anti-inflammatory cytokine responses in pregnancy and lactation. Clin Exp Immunol 144, 392400.
20Hoglen, NC, Abril, EA, Sauer, JM, et al. (1997) Modulation of Kupffer cell and peripheral blood monocyte activity by in vivo treatment of rats with all-trans-retinol. Liver 17, 157165.
21Maynard, CL, Hatton, RD, Helms, WS, et al. (2009) Contrasting roles for all-trans retinoic acid in TGF-beta-mediated induction of Foxp3 and Il10 genes in developing regulatory T cells. J Exp Med 206, 343357.
22Iwata, M, Eshima, Y & Kagechika, H (2003) Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors. Int Immunol 15, 10171025.
23Damsgaard, CT, Lauritzen, L, Calder, PC, et al. (2009) Whole-blood culture is a valid low-cost method to measure monocytic cytokines – a comparison of cytokine production in cultures of human whole-blood, mononuclear cells and monocytes. J Immunol Methods 340, 95101.
24Seguin-Devaux, C, Hanriot, D, Dailloux, M, et al. (2005) Retinoic acid amplifies the host immune response to LPS through increased T lymphocytes number and LPS binding protein expression. Mol Cell Endocrinol 245, 6776.
25Coutsoudis, A, Kiepiela, P, Coovadia, HM, et al. (1992) Vitamin A supplementation enhances specific IgG antibody levels and total lymphocyte numbers while improving morbidity in measles. Pediatr Infect Dis J 11, 203209.
26Ueki, S, Mahemuti, G, Oyamada, H, et al. (2008) Retinoic acids are potent inhibitors of spontaneous human eosinophil apoptosis. J Immunol 181, 76897698.
27Ahmad, SM, Haskell, MJ, Raqib, R, et al. (2009) Markers of innate immune function are associated with vitamin a stores in men. J Nutr 139, 377385.
28Casimir, GJ, Mulier, S, Hanssens, L, et al. (2010) Gender differences in inflammatory markers in children. Shock 33, 258262.

Keywords

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

  • Mathias J. Jørgensen (a1), Ane B. Fisker (a2), Erliyani Sartono (a3), Andreas Andersen (a1) (a2), Christian Erikstrup (a4), Ida M. Lisse (a4), Maria Yazdanbakhsh (a3), Peter Aaby (a1) (a2) and Christine S. Benn (a1) (a2)...

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