BACKGROUND Anti-Tumor Necrosis Factor-alpha therapy has become clinically important for treating inflammatory bowel disease. However, the use of conventional immunotherapy requires a systemic exposure of patients and collateral side effects. Lactic acid bacteria have been shown to be effective as mucosal delivering system for cytokine and single domain antibodies, and it is amenable to clinical purposes. Therefore, lactic acid bacteria may function as vehicles for delivery of therapeutic antibodies molecules to the gastrointestinal tract restricting the pharmacological effect towards the gut. Here, we use the mucosal delivery of Lactococcus lactis carrying an anti-TNFα scFv expression plasmid on a DSS-induced colitis model in mice. RESULTS Experimental colitis was induced with DSS administered in drinking water. L. lactis carrying the scFv expression vector was introduced by gavage. After four days of treatment, animals showed a significant improvement in histological score and disease activity index compared to those of untreated animals. Moreover, treated mice display IL-6, IL17A, IL1β, IL10 and FOXP3 mRNA levels similar to health control mice. Therefore, morphological and molecular markers suggest amelioration of the experimentally induced colitis. CONCLUSION These results provide evidence for the use of this alternative system for delivering therapeutic biopharmaceuticals in loco for treating inflammatory bowel disease, paving the way for a novel low-cost and site-specific biotechnological route for the treatment of inflammatory disorders.

中文翻译：

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携带抗TNF scFv表达载体的乳酸乳球菌的粘膜递送改善了小鼠的实验性结肠炎。

背景技术抗肿瘤坏死因子-α疗法对于治疗炎性肠病已经在临床上变得重要。然而，常规免疫疗法的使用要求患者全身暴露和附带副作用。乳酸菌已被证明是有效的细胞因子和单结构域抗体的粘膜递送系统，并且适合于临床目的。因此，乳酸菌可以充当将治疗性抗体分子递送至胃肠道的媒介物，从而限制了对肠道的药理作用。在这里，我们在DSS诱导的结肠炎模型中使用携带抗TNFαscFv表达质粒的乳酸乳球菌的粘膜递送。结果实验性结肠炎是通过在饮用水中给予DSS诱导的。L. 通过管饲法引入携带scFv表达载体的乳酸。治疗四天后，与未治疗的动物相比，动物的组织学评分和疾病活动指数显着改善。此外，与健康对照小鼠相似，经治疗的小鼠显示IL-6，IL17A，IL1β，IL10和FOXP3 mRNA水平。因此，形态学和分子标志物提示了实验性结肠炎的改善。结论这些结果为该替代系统用于局部递送治疗性生物药物治疗炎性肠病提供了证据，为新型低成本和针对特定部位的炎性疾病治疗生物技术路线铺平了道路。与未治疗的动物相比，这些动物在组织学评分和疾病活动指数方面显示出显着的改善。此外，与健康对照小鼠相似，经治疗的小鼠显示IL-6，IL17A，IL1β，IL10和FOXP3 mRNA水平。因此，形态学和分子标志物提示了实验性结肠炎的改善。结论这些结果为该替代系统用于局部递送治疗性生物药物治疗炎性肠病提供了证据，为新型低成本和针对特定部位的炎性疾病生物技术途径铺平了道路。与未治疗的动物相比，这些动物在组织学评分和疾病活动指数方面显示出显着改善。此外，与健康对照小鼠相似，治疗的小鼠显示IL-6，IL17A，IL1β，IL10和FOXP3 mRNA水平。因此，形态学和分子标志物提示了实验性结肠炎的改善。结论这些结果为该替代系统用于局部递送治疗性生物药物治疗炎性肠病提供了证据，为新型低成本和针对特定部位的炎性疾病治疗生物技术路线铺平了道路。形态学和分子标志物提示实验性结肠炎的改善。结论这些结果为该替代系统用于局部递送治疗性生物药物治疗炎性肠病提供了证据，为新型低成本和针对特定部位的炎性疾病治疗生物技术路线铺平了道路。形态学和分子标记提示实验性结肠炎的改善。结论这些结果为该替代系统用于局部递送治疗性生物药物治疗炎性肠病提供了证据，为新型低成本和针对特定部位的炎性疾病治疗生物技术路线铺平了道路。