Buck Rachael H, Thomas Debra L, Winship Timothy R, Cordle Christopher T, Kuchan Matthew J, Baggs Geraldine E, Schaller Joseph P, Wheeler J Gary
Abbott Laboratories, Ross Products Division, 3300 Stelzer Rd., Columbus, OH 43219, USA.
Pediatr Res. 2004 Dec;56(6):891-900. doi: 10.1203/01.PDR.0000145577.03287.FA. Epub 2004 Oct 20.
The objective of this study was to determine whether dietary ribonucleotides alter immune cell phenotypes or function in the first year of life. Newborn term infants in a double-blind, 12-mo, multicenter trial were randomized to cow milk formula groups with (FN, n = 138) or without (F, n = 147) 72 mg/L supplemental ribonucleotides. A nonrandomized HMF cohort (n = 192) was concurrently enrolled. Eighty-eight immune blood cell types were characterized by flow cytometry. Data were analyzed by multivariate ANOVA (MANOVA), ANOVA, and repeated measures analysis (RMA), with adjustments made for multiple comparisons. Ribonucleotide feeding changed subpopulations of T and natural killer (NK) cells. FN had higher numbers and percentages of memory/effector (M/E) cytotoxic/suppressor (CD45R0(+)CD8(+), RMA) T, Fas(+) M/E (CD45R0(+)CD95(+)CD3(+), 6 mo) T, and CD56(+)CD16(-) NK cells (CD56(+)CD16(-)CD3(-)CD8(-), 12 mo), and higher percentages of M/E helper (CD45R0(+)CD4(+), RMA) T, Tc1 (IFN gamma(+)CD4(-)CD3(+), RMA), total interferon (IFN)gamma T (IFN gamma(+)CD4(+/-)CD3(+), RMA), Th2 (IL-4(+)CD4(+)CD3(+), 7 mo), and CD57(+) NK-T cells (CD57(+)CD56(-)CD3(+), 6 mo, 7 mo) compared with F. Percentages of naive helper T (CD45RA(+)CD4(+), 12 mo) and numbers and percentages of CD56(+) NK-T cells (CD56(+)CD16(-)CD3(+)CD8(-), 2 mo, 6 mo) were lower in FN than F. Percentages of M/E cytotoxic/suppressor, Th2, and CD56(+)CD16(-) NK cells in FN were significantly higher than F but were not different from HMF, whereas F was significantly lower than HMF. Ribonucleotide supplementation of infant formula supported increased T-cell maturation and affected immunoregulatory NK cell subsets. These FN-associated immune cell profiles either did not differ from those infants fed HMF or tended to be more like those fed HMF than those fed F.
本研究的目的是确定膳食核糖核苷酸是否会改变生命第一年中免疫细胞的表型或功能。在一项为期12个月的多中心双盲试验中,足月新生儿被随机分为添加(FN,n = 138)或不添加(F,n = 147)72 mg/L补充核糖核苷酸的牛奶配方奶粉组。同时纳入了一个非随机的水解配方奶粉队列(n = 192)。通过流式细胞术对88种免疫血细胞类型进行了表征。数据采用多变量方差分析(MANOVA)、方差分析(ANOVA)和重复测量分析(RMA)进行分析,并对多重比较进行了校正。喂养核糖核苷酸改变了T细胞和自然杀伤(NK)细胞的亚群。与F组相比,FN组记忆/效应(M/E)细胞毒性/抑制性(CD45R0(+)CD8(+),RMA)T细胞、Fas(+) M/E(CD45R0(+)CD95(+)CD3(+),6个月)T细胞和CD56(+)CD16(-) NK细胞(CD56(+)CD16(-)CD3(-)CD8(-),12个月)的数量和百分比更高,M/E辅助性(CD45R0(+)CD4(+),RMA)T细胞、Tc1(IFNγ(+)CD4(-)CD3(+),RMA)、总干扰素(IFN)γ T细胞(IFNγ(+)CD4(+/-)CD3(+),RMA)、Th2(IL-4(+)CD4(+)CD3(+),7个月)和CD57(+) NK-T细胞(CD57(+)CD56(-)CD3(+),6个月、7个月)的百分比更高。与F组相比,FN组中幼稚辅助性T细胞(CD45RA(+)CD4(+),12个月)的百分比以及CD56(+) NK-T细胞(CD56(+)CD16(-)CD3(+)CD8(-),2个月、6个月)的数量和百分比更低。FN组中M/E细胞毒性/抑制性、Th2和CD56(+)CD16(-) NK细胞的百分比显著高于F组,但与水解配方奶粉组无差异,而F组显著低于水解配方奶粉组。婴儿配方奶粉中添加核糖核苷酸有助于T细胞成熟增加,并影响免疫调节性NK细胞亚群。这些与FN相关的免疫细胞谱与食用水解配方奶粉的婴儿的谱无差异,或者相比于食用F组配方奶粉的婴儿,更倾向于与食用水解配方奶粉的婴儿相似。