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

Abstract

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.