Avaliação dos efeitos da terapia biológica com infliximabe na colite de exclusão

Abstract

Introduction: Diversion colitis (DC) is a chronic inflammatory process that develops in the mucosa of the colonic segments devoid of fecal stream. The increase in the production of reactive oxygen species and inflammatory cytokines in these segments suggests that the DC has etiopathogenic molecular mechanisms like what occurs in IBD. While the use of anti-TNF-α antibodies, particularly infliximab, represents one of the most effective therapeutic strategies for the treatment of IBD, little is known about the effect of infliximab in the treatment of DC, human or experimental. Objective: To evaluate the effects of infliximab therapy on inflammation and tissue content of TNFα in the colic mucosa of rats, with or without fecal stream. Method: Twenty-two male Wistar rats underwent intestinal diversion by making a proximal terminal colostomy and closing of the distal stump (Hartmann procedure). The animals remained for 12 weeks with intestinal derivation for the development of DC in the excluded segment.Then, they were divided into three experimental groups, as submitted, weekly, to subcutaneous application of saline (2ml/week) or infliximab at the dosages of 5mg/kg /week and 10mg/kg/week, for five consecutive weeks. After this period, the animals were euthanized and segments of the colon, with and without fecal stream, were removed. Histopathological changes and the intensity of the inflammatory process were assessed by histological study hematoxylin-eosin staining. The inflammatory tissue grade was assessed considering the intensity of epithelial atrophy, epithelial loss, presence of abscesses in the colonic glands, leukocyte infiltrate, and number of goblet cells, being stratified according to a previously validated scale. The tissue content of TNF-α in colic segments was evaluated by its tissue expression, identified by immunohistochemical study. Results: Segments without fecal stream had a higher inflammatory score when compared to segments with fecal stream, regardless of the intervention substance, as well as the infliximab dosage used. The infliximab intervention significantly reduced the inflammatory score in the segments without fecal stream. Higher tissue content of TNF-α was found in segments without fecal stream, regardless of the experimental group considered. The application of infliximab did not modify the tissue content of TNF-α, in segments without intestinal stream, regardless of the dosage used. Conclusions: In the experimental DC model used, the subcutaneous application of infliximab decreased the inflammatory process in the mucosa devoid of fecal stream, despite not reducing the tissue content of TNFα.