Long Kurt Z, Estrada-Garcia Teresa, Rosado Jorge L, Ignacio Santos Jose, Haas Meredith, Firestone Mathew, Bhagwat Jui, Young Cheryl, DuPont Herbert L, Hertzmark Ellen, Nanthakumar Nanda N
Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
J Nutr. 2006 May;136(5):1365-70. doi: 10.1093/jn/136.5.1365.
Vitamin A supplementation has consistently reduced infant mortality and the severity of pathogen-induced diarrhea. The mechanism by which vitamin A modulates the mucosal immune response to produce these effects remains poorly defined. To address this issue, stools collected during the summer months from 127 Mexican children 5-15 mo old enrolled in a larger, randomized, double-blind, placebo-controlled, vitamin A supplementation trial were screened for interleukin (IL)-4, IL-6, interferon-gamma (IFN-gamma), and gastrointestinal pathogens. Fecal cytokine values were categorized into 3 levels (undetectable, <median, > or =median). Multinomial regression models were used to determine the probability that vitamin A-supplemented children had higher categorical values of a cytokine than children in the placebo group. Differences in categorical values were also analyzed after stratification by gastrointestinal pathogen infections and diarrheal symptoms. Overall, fecal cytokine categorical levels did not differ between children randomized to the 2 arms. Vitamin A-supplemented children infected with enteropathogenic E. coli (EPEC) had reduced IL-4 and IFN-gamma levels [odds ratio (OR) = 0.3, 95% CI 0.13-0.67 and OR = 0.34, 95% CI 0.14-0.83, respectively] compared with children in the placebo group. Vitamin A-supplemented children had increased IL-4 levels when infected with A. lumbricoides (OR = 12.06, 95% CI 0.95-153.85). In contrast, IL-4 levels increased (OR = 2.14, 95% CI 0.94-4.87) and IFN-gamma levels decreased (OR = 0.51, 95% CI 0.26-0.99) among vitamin A-supplemented children with diarrhea compared with children in the placebo group. These findings suggest that the regulation of the mucosal immune response by vitamin A may depend on the type of enteric pathogen infecting the child and the presence of clinical symptoms.
补充维生素A一直能够降低婴儿死亡率以及病原体引发腹泻的严重程度。维生素A调节黏膜免疫反应以产生这些效果的机制仍不清楚。为解决这一问题，在一项规模更大的随机、双盲、安慰剂对照的补充维生素A试验中，对127名年龄在5至15个月的墨西哥儿童在夏季收集的粪便进行白细胞介素（IL）-4、IL-6、干扰素-γ（IFN-γ）和胃肠道病原体筛查。粪便细胞因子值分为3个水平（检测不到、<中位数、≥中位数）。采用多项回归模型来确定补充维生素A的儿童细胞因子分类值高于安慰剂组儿童的概率。在按胃肠道病原体感染和腹泻症状分层后，也对分类值的差异进行了分析。总体而言，随机分配到两组的儿童粪便细胞因子分类水平没有差异。与安慰剂组儿童相比，感染肠致病性大肠杆菌（EPEC）的补充维生素A的儿童IL-4和IFN-γ水平降低[优势比（OR）分别为0.3，95%置信区间0.13 - 0.67和OR = 0.34，95%置信区间0.14 - 0.83]。感染蛔虫的补充维生素A的儿童IL-4水平升高（OR = 12.06，95%置信区间0.95 - 153.85）。相比之下，与安慰剂组儿童相比，腹泻的补充维生素A的儿童中IL-4水平升高（OR = 2.14，95%置信区间0.94 - 4.87），IFN-γ水平降低（OR = 0.51，95%置信区间0.26 - 0.99）。这些发现表明，维生素A对黏膜免疫反应的调节可能取决于感染儿童的肠道病原体类型以及临床症状的存在。
