Benlounes N, Dupont C, Candalh C, Blaton M A, Bloom M, Heyman M
INSERM U290, Hôpital St-Lazare, Paris, France.
Clin Exp Allergy. 1997 Aug;27(8):942-8.
In infants with cow's milk allergy and intestinal symptoms, peripheral blood mononuclear cells stimulated in vitro with cow's milk proteins, secrete large amounts of the proinflammatory cytokine TNF alpha thus altering intestinal barrier capacity. Terfenadine, an antihistaminic drug, inhibits the release of several inflammatory mediators, including histamine, prostaglandins and leukotrienes.
To test the potential ability of terfenadine to inhibit TNF alpha secretion by mononuclear cells from infants with cow's milk allergy.
Mononuclear cells from infants allergic to cow's milk proteins were stimulated in vitro for 6 days by a mixture of milk proteins (beta-lactoglobulin, alpha-lactalbumin and casein) with or without terfenadine (0.1-1 microM) and culture supernatants were assayed for TNF alpha by enzyme immunoassay. The effect of culture supernatants on intestinal barrier capacity was evaluated by measuring the electrical resistance (index of integrity) of filter-grown HT29-19 A intestinal cells in Ussing chambers.
During active cow's milk allergy, mononuclear cells stimulated with cow's milk proteins secreted large amounts of TNF alpha which significantly reduced the electrical resistance of HT29-19 A intestinal cells. There was a dose-dependent decrease in TNF alpha secretion in the presence of terfenadine, with a maximal inhibition of 62% of this secretion at 1 microM. Accordingly, terfenadine-treated mononuclear cells supernatants did not alter the electrical resistance of intestinal HT29.19 A cells.
These results indicate that in infants with intestinal dysfunction due to cow's milk allergy, terfenadine is a potent inhibitor of the TNF alpha secretion induced by sensitizing milk protein antigens. This inhibition prevents the degradation of intestinal function as measured in an intestinal cell line, in vitro.
在患有牛奶过敏和肠道症状的婴儿中，外周血单核细胞在体外用牛奶蛋白刺激后，会分泌大量促炎细胞因子肿瘤坏死因子α（TNFα），从而改变肠道屏障功能。特非那定是一种抗组胺药物，可抑制包括组胺、前列腺素和白三烯在内的多种炎症介质的释放。
测试特非那定抑制牛奶过敏婴儿单核细胞分泌TNFα的潜在能力。
用或不用特非那定（0.1 - 1微摩尔），将牛奶蛋白（β-乳球蛋白、α-乳白蛋白和酪蛋白）混合物在体外刺激对牛奶蛋白过敏的婴儿的单核细胞6天，并用酶免疫测定法检测培养上清液中的TNFα。通过测量Ussing室中滤膜生长的HT29 - 19A肠细胞的电阻（完整性指标）来评估培养上清液对肠道屏障功能的影响。
在牛奶过敏活动期，用牛奶蛋白刺激的单核细胞分泌大量TNFα，这显著降低了HT29 - 19A肠细胞的电阻。在特非那定存在的情况下，TNFα分泌呈剂量依赖性下降，在1微摩尔时最大抑制率为该分泌的62%。因此，用特非那定处理的单核细胞上清液不会改变肠道HT29.19A细胞的电阻。
这些结果表明，在因牛奶过敏导致肠道功能障碍的婴儿中，特非那定是致敏牛奶蛋白抗原诱导的TNFα分泌的有效抑制剂。这种抑制作用可防止体外在肠细胞系中测得的肠道功能退化。
