Anti-inflammatory properties of IL-10 producing Lactococcus lactis using the xylose inducible expression system.

DEL CARMEN, S.; DE MORENO DE LEBLANC, A.; MIYOSHI, A.; AZEVEDO, V.; LEBLANC, J. G.

Foz do Iguaçu, Brazil

Congreso; 26º Congresso Brasileiro de Microbiologia; 2011

Sociedade Brasileira de Microbiologia

Interleukin-10 (IL-10) is the most important anti-inflammatory cytokine and can be used in the treatment of different intestinal inflammatory diseases. Oral treatment with IL-10 is difficult because of its sensitivity to the harsh conditions in the gastrointestinal tract, and systemic treatments are related to undesirable side effects. Oral administration of Lactococcus (L.) lactis producing IL-10 under the control of the xylose inducible expression system (XIES) could be an alternative for the delivery of this important cytokine. The aim of this study was to develop a fermented milk product using a strain of L. lactis that produces IL-10 under the control of the XIES and evaluate its anti-inflammatory effect using a murine model. Two genetically engineered strains of L. lactis NCDO2118 harboring the XIES to target rodent IL-10 to the cytoplasm (Cyt strain) or to the extracellular medium (Sec strain) were used to ferment milk containing 1% xylose. The anti-inflammatory potential of the fermented milk products was evaluated using a trinitrobenzene sulfonic acid (TNBS) induced Crohn’s disease model. Microbial translocation to liver, macroscopic and histological damage of the intestines and cytokine production profiles in fluids and tissues were evaluated in different experimental groups. Mice that received milks fermented by L. lactis strains producing IL-10 in the cytoplasm (Cyt strain) or secreted to the product (Sec strain) possessed anti-inflammatory properties as shown by lower damage scores in their large intestines, decreased IFN-gamma levels in their intestinal fluids and lower translocation to liver, compared to mice receiving milk fermented by the wild-type (Wt) strain or those not receiving any treatment. The use of fermented milks as a new form of administration of IL-10 producing L. lactis under the control of the XIES was effective in the prevention of inflammation using a murine model of Crohn’s disease. These results could lead to the development of novel therapeutical products.