Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin, Berlin, Germany.
Int Arch Allergy Immunol. 2011;156(2):196-204. doi: 10.1159/000322352. Epub 2011 May 18.
Modulating early immune response by application of bacteria and their by-products has been suggested as a preventive strategy against the development of allergic diseases. In light of this, the aim of the study was to test the effects of oral administration of bacterial lysates (BL) in a rat model of food allergy.
BL or PBS were administered orally to neonatal Brown Norway rats up to an age of 42 days. Additionally, animals were sensitized 3 times (days 35, 40 and 45) intraperitoneally with ovalbumin (OVA). On days 60 and 61, rats were locally challenged with OVA by gavage feeding.
Detection of increased allergen-specific Ig serum levels and proliferative responses of spleen mononuclear cells confirmed systemic sensitization. In serum of animals that received BL in addition to OVA sensitization, the levels of allergen-specific IgE and IgG were significantly reduced compared to animals which were not exposed to BL. Allergen-stimulated lymphocytes from spleen and mesenteric lymph nodes of BL-treated animals showed a significantly elevated cytokine production of IL-10. To assess local functional changes of the intestinal barrier we measured the intestinal permeability, which was increased in OVA-sensitized and challenged animals compared to nonsensitized controls, yet significantly reduced in sensitized animals which received BL.
These data suggest that local administration of BL (pathogen-associated molecular patterns) in the intestine exhibits immuno-modulating effects. Furthermore, pathophysiological features of food allergy, such as the loss of gut mucosal integrity, might be reduced by the treatment with BL.
通过应用细菌及其产物来调节早期免疫反应,被认为是预防过敏性疾病发展的一种策略。有鉴于此,本研究的目的是在食物过敏的大鼠模型中测试口服细菌裂解物(BL)的效果。
BL 或 PBS 被口服给予新生的布朗挪威大鼠,直至 42 天大。此外,动物还通过腹膜内注射卵清蛋白(OVA)进行了 3 次致敏(第 35、40 和 45 天)。在第 60 和 61 天,通过灌胃法用 OVA 对大鼠进行局部挑战。
检测到过敏原特异性 Ig 血清水平升高和脾单核细胞的增殖反应证实了全身致敏。在接受 BL 加 OVA 致敏的动物的血清中,过敏原特异性 IgE 和 IgG 的水平与未暴露于 BL 的动物相比显著降低。来自接受 BL 处理的动物的脾和肠系膜淋巴结的过敏原刺激淋巴细胞显示出显著增加的 IL-10 细胞因子产生。为了评估肠道屏障的局部功能变化,我们测量了肠道通透性,与未致敏对照相比,OVA 致敏和挑战的动物的肠道通透性增加,但接受 BL 处理的致敏动物的肠道通透性显著降低。
这些数据表明,BL(病原体相关分子模式)在肠道中的局部给药具有免疫调节作用。此外,BL 治疗可能会降低食物过敏的病理生理特征,例如肠道黏膜完整性的丧失。