Inflammatory bowel diseases (IBD) are intestinal disorders characterized by inflammation in the gastrointestinal tract (GIT) and to date, no efficient treatments exist. Interleukin-10 (IL-10), one of the most important anti-inflammatory cytokines of the immune response, has been under study due to its potential for IBD therapy; however, systemic treatments lead to undesirable side effects and oral administration is limited due to its quick degradation. To avoid these bottlenecks, we previously engineered an invasive Lactococcus lactis (L. lactis) strain capable of delivering, directly to host cells, a eukaryotic DNA expression vector coding for IL-10 of Mus musculus (pValac:il-10) that diminished inflammation in two induced mouse models of intestinal inflammation. Thus, the aim of this study was to analyze its therapeutic effect in the IL-10-deficient mouse model (IL-10−/−) that spontaneously and gradually develops an inflammation that modifies the immune system and resembles Crohn’s disease (CD) in humans, and evaluate if it would also diminish and/or prevent the onset of this disease. Oral administration of L. lactis MG1363 FnBPA+ (pValac:il-10) to IL-10−/− mice not only led to IL-10 production by these, but consequently also diminished the severe development of the disease, with animals showing lower macroscopic scores and histological damages, increased IL-10 levels and tendency to lower pro-inflammatory cytokine levels. The results of this study, together with the previously published ones using this DNA delivery-based strategy, show that it is capable of creating and maintaining an anti-inflammatory environment in the GIT and thus effectively diminish the onset of inflammation in various mouse models.

中文翻译：

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携带乳酸乳球菌菌株的质粒可减轻IL-10缺陷小鼠的肠道炎症。

炎性肠病（IBD）是肠胃疾病，其特征在于胃肠道（GIT）发炎，迄今为止，尚无有效的治疗方法。白细胞介素10（IL-10）是免疫反应中最重要的抗炎细胞因子之一，由于其具有IBD治疗的潜力，因此正在研究中。然而，全身治疗导致不良副作用，并且由于其快速降解而限制了口服给药。为避免这些瓶颈，我们之前设计了一种侵害性乳酸乳球菌（L. lactis）菌株，该菌株能够直接向宿主细胞传递编码小家鼠IL-10（pValac：il-10）的真核DNA表达载体，从而减少炎症在两种诱导的小鼠肠道炎症模型中 从而，这项研究的目的是分析其在IL-10-缺陷型小鼠模型（IL-10-/-）中的治疗效果，该模型可自发并逐渐发展出可改变免疫系统并类似于人类克罗恩病（CD）的炎症，并评估它是否还会减少和/或预防这种疾病的发作。向IL-10-/-小鼠口服乳酸乳球菌MG1363 FnBPA +（pValac：il-10）不仅导致它们产生IL-10，而且还减少了疾病的严重发展，动物表现出较低的肉眼观察评分和组织学损害，IL-10水平升高以及促炎细胞因子水平降低的趋势。这项研究的结果以及以前发表的使用这种基于DNA递送的策略的结果，