Jensen Kristoffer J, Søndergaard Mia J, Andersen Andreas, Martins Cesario, Erikstrup Christian, Aaby Peter, Flanagan Katie L, Benn Christine Stabell
1Research Center for Vitamins and Vaccines,Bandim Health Project,Statens Serum Institut,DK-2300 Copenhagen,Denmark.
2Bandim Health Project,Indepth Network,Bissau,Bissau codex 1004,Guinea-Bissau.
Br J Nutr. 2017 Dec;118(11):942-948. doi: 10.1017/S0007114517002938. Epub 2017 Nov 23.
High-dose vitamin A supplementation (VAS) may affect mortality to infectious diseases in a sex-differential manner. Here, we analysed the long-term immunological effects of neonatal vitamin A supplementation (NVAS) in 247 children, who had been randomly allocated to 50 000 or 25 000 IU vitamin A (15mg and 7·5mg retinol equivalents, respectively) or placebo at birth. At 4-6 months of age, we assessed bacille Calmette-Guérin (BCG) scarification, and we analysed in vitro responses of TNF-α, IL-5, IL-10, IL-13 and IFN-γ in whole blood stimulations to phytohaemagglutinin (PHA), purified protein derivative (PPD), tetanus toxoid and lipopolysaccharide. There were no differences between the two doses of NVAS, and thus they were analysed combined as NVAS (any dose) v. placebo. All analyses were performed unstratified and by sex. NVAS increased the chance of having a scar after BCG vaccination in females (NVAS v. placebo: 96 v. 71 %, proportion ratio: 1·24; 95 % CI 1·09, 1·42), but not in males (P for interaction=0·012). NVAS was associated with significant sex-differential effects on the pro- to anti-inflammatory cytokine ratios (TNF-α:IL-10) to PPD, tetanus toxoid and medium alone, which were increased in females but decreased in males. In addition, IL-17 responses tended to be increased in NVAS v. placebo recipients in males but not in females, significantly so for the PHA stimulation. The study corroborates sex-differential effects of VAS on the immune system, emphasising the importance of analysing VAS effects by sex.
大剂量维生素A补充剂（VAS）可能以性别差异的方式影响传染病死亡率。在此，我们分析了247名儿童新生儿期维生素A补充剂（NVAS）的长期免疫效应，这些儿童在出生时被随机分配接受50000或25000国际单位维生素A（分别为15毫克和7.5毫克视黄醇当量）或安慰剂。在4至6个月大时，我们评估了卡介苗（BCG）划痕接种情况，并分析了全血刺激对植物血凝素（PHA）、纯化蛋白衍生物（PPD）、破伤风类毒素和脂多糖的体外TNF-α、IL-5、IL-10、IL-13和IFN-γ反应。两种剂量的NVAS之间没有差异，因此将它们合并分析为NVAS（任何剂量）与安慰剂组。所有分析均未分层且按性别进行。NVAS增加了女性接种BCG疫苗后出现疤痕的几率（NVAS与安慰剂组：96%对71%，比例比：1.24；95%置信区间1.09，1.42），但男性中未出现这种情况（交互作用P值=0.012）。NVAS对PPD、破伤风类毒素和单独培养基的促炎与抗炎细胞因子比值（TNF-α:IL-10）有显著的性别差异效应，女性中升高而男性中降低。此外，NVAS组男性对PHA刺激的IL-17反应倾向于高于安慰剂组，而女性中未出现这种情况，PHA刺激时差异显著。该研究证实了VAS对免疫系统的性别差异效应，强调了按性别分析VAS效应的重要性。
