Avaliação dos efeitos terapêuticos de Lactococcus lactis carreadora do vetor de expressão eucariótica que codifica para scFv anti-TNFa em modelo de colite induzida por TNBS

Abstract

Crohn’s disease (CD) belongs to the group of infectious intestinal diseases (IBD), and is characterized by an intestinal infection caused by severe infections of the mucosa, which cannot be cured by clinical or surgical treatment and which can affect the entire gastrointestinal tract. TNF-α plays a fundamental role in the disease, being considered the best therapeutic target. However, an intravenous route of immunotherapies causes immunogenicity and systemic effects. To circumvent these restrictions, local delivery of these drugs could benefit patients, restrict therapy to the inflammatory site. The development of Lactococcus lactis cephas is capable of providing a eukaryotic expression vector that encodes a single chain variable fragment (scFv) of antibody represents a new strategy for the analysis of a more effective alternative therapy for isolated expression in the intestine, against CD. In this way, the objective of this work was to evaluate the therapeutic effects of fragments of scFv use anti-TNF-α used locally in the intestinal mucosa using L. lactis as a vehicle for delivery of vectors in the intestinal mucosa, in the experimental Crohn's disease model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Thus, the effect of producing these filters directly on the intestinal mucosa was analyzed. Female BALB c mice were used, with experimental colitis induction by TNBS for four weeks. The L. lactis culture was administered orally in the last 5 days of the protocol. No day after the last day of treatment, the animals were sacrificed and with different temperature variations. He observed an improvement in the group treated with L. lactis FnBPA + (pValac :: anti-TNFα) in the macroscopic parameters of the disease in relation to the unused groups. In the histological analysis, the beneficial effect of the treatment was better observed in the proximal region, with reduction of the inflammatory infiltrate and maintenance of the mucous layer. With these results, we conclude the treatment with pValac :: anti-TNFα has a mitigating effect on the experimental collection model, and the most recent studies are adequate to elucidate the molecular mechanisms used by the effect and, thus demonstrating a strategy based on in delivering DNA.