Attenuation of intestinal inflammation in IL-10 deficient mice by a plasmid carrying Lactococcus lactis strain

Background 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. Results 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. Conclusions 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.