Rautava Samuli, Isolauri Erika
Department of Paediatrics, University of Turku, Turku, Finland.
J Pediatr Gastroenterol Nutr. 2004 Nov;39(5):529-35. doi: 10.1097/00005176-200411000-00015.
A failure in the establishment and maintenance of oral tolerance in infancy may result in food allergy. To further assess the role of the intestinal immune system in cow's milk allergy (CMA), we investigated the systemic production of the pro-allergenic Th2 cytokine interleukin (IL)-4 and anti-allergenic cytokines IL-10, transforming growth factor (TGF)-beta1 and TGF-beta2 in infants suffering from atopic eczema with and without CMA during antigen elimination diet and oral antigen exposure.
18 infants (mean age, 9.6 months; 95% confidence interval 8.1-11.1 months) with atopic eczema and CMA and 17 infants (mean age, 9.7 months; 95% confidence interval 8.6-10.9 months) with atopic eczema tolerant to milk as assessed by a double blind, placebo-controlled cow's milk challenge were investigated. Peripheral blood mononuclear cells were obtained during antigen elimination diet and during oral cow's milk challenge and stimulated with Concanavalin-A or cow's milk or were left unstimulated. The cytokine concentrations were measured by enzyme-linked immunosorbent assay.
During antigen elimination, the Concanavalin A-stimulated production of TGF-beta2 was significantly lower in infants with CMA as compared with infants without CMA: 129 pg/mL (interquartile ratio, 124-144 pg/mL) vs. 149 pg/mL (interquartile ratio, 133-169 pg/mL); P = 0.016. During oral antigen exposure, the immune responses in infants with CMA were characterized by significantly higher spontaneous production of IL-4 as compared with those without CMA: 12.0 pg/mL (interquartile ratio, 5.2-28.3 pg/mL) vs. 4.2 pg/mL (interquartile ratio, 1.5-7.6 pg/mL); P = 0.018.
Infants with atopic eczema and CMA exhibit markedly increased systemic pro-allergenic IL-4 responses on intestinal antigen contact, which may partially be explained by a defective ability to launch anti-allergenic TGF-beta2 responses.
婴儿期口服耐受的建立和维持失败可能导致食物过敏。为了进一步评估肠道免疫系统在牛奶过敏(CMA)中的作用,我们调查了在抗原清除饮食和口服抗原暴露期间,患有和未患有CMA的特应性湿疹婴儿体内促变应原性Th2细胞因子白细胞介素(IL)-4以及抗变应原性细胞因子IL-10、转化生长因子(TGF)-β1和TGF-β2的全身产生情况。
研究了18名患有特应性湿疹和CMA的婴儿(平均年龄9.6个月;95%置信区间8.1 - 11.1个月)以及17名经双盲、安慰剂对照牛奶激发试验评估对牛奶耐受的特应性湿疹婴儿(平均年龄9.7个月;95%置信区间8.6 - 10.9个月)。在抗原清除饮食期间和口服牛奶激发期间获取外周血单个核细胞,并用刀豆球蛋白-A或牛奶刺激,或不进行刺激。通过酶联免疫吸附测定法测量细胞因子浓度。
在抗原清除期间,与未患CMA的婴儿相比,患CMA的婴儿经刀豆球蛋白A刺激后TGF-β2的产生显著降低:129 pg/mL(四分位间距,124 - 144 pg/mL)对149 pg/mL(四分位间距,133 - 169 pg/mL);P = 0.016。在口服抗原暴露期间,与未患CMA的婴儿相比,患CMA的婴儿的免疫反应表现为IL-4的自发产生显著更高:12.0 pg/mL(四分位间距,5.2 - 28.3 pg/mL)对4.2 pg/mL(四分位间距,1.5 - 7.6 pg/mL);P = 0.018。
患有特应性湿疹和CMA的婴儿在肠道抗原接触时表现出全身促变应原性IL-4反应明显增加,这可能部分归因于启动抗变应原性TGF-β2反应的能力缺陷。