Dextran sulphate sodium colitis in C57BL/6J mice is alleviated by Lactococcus lactis and worsened by the neutralization of Tumor necrosis Factor alpha

摘要

TNF alpha has a well-established role in inflammatory bowel disease that affects the gastrointestinal tract and is usually manifested as Crohn's disease or ulcerative colitis. We have compared Lactococcus lactis NZ9000 displaying TNF alpha-binding affibody with control Lactococcus lactis and with anti-TNF alpha antibody infliximab for the treatment of mice with dextran sulphate sodium (DSS)-induced colitis. L. lactis NZ9000 alleviated the colitis severity one week after colitis induction with DSS, more effectively when administered in preventive fashion prior to, during and after DSS administration. TNF alpha-binding L lactis was less effective than control L lactis, particularly when TNF alpha-binding L. lactis was administered in preventive fashion. Similarly, an apparently detrimental effect of TNF alpha neutralization was observed in mice that were intraperitoneally administered anti-TNF alpha monoclonal antibody infliximab prior to colitis induction. The highest concentrations of tissue TNF alpha were observed in groups without DSS colitis that were treated either with TNF alpha-binding L. lactis or infliximab. To conclude, we have confirmed that L. lactis exerts a protective effect on DSS-induced colitis in mice. Contrary to expectations, but in line with some reports, the neutralization of TNF alpha aggravated disease symptoms in the acute phase of colitis and increased TNF alpha concentration in colon tissue of healthy mice. Nevertheless, we have demonstrated that oral administration of bacteria with surface displayed TNF alpha-binding affibody can interfere significantly with TNF alpha signaling and mimic the infliximab response in the given animal model of colitis. (C) 2016 Elsevier B.V. All rights reserved.