Avaliação da atividade imunomoduladora de diferentes subpopulações de macrófagos na mucosite intestinal induzida por 5-fluorouracil

Abstract

5-Fluorouracil has been used as an effective chemotherapy agent for more than 40 years, but is considered a controversial drug because it causes serious side effects such as mucositis. Mucositis is a serious condition of the mucosa of the gastrointestinal tract, related to direct damage to epithelial cells and inflammation resulting from the use of chemotherapy or radiotherapy. It mainly affects the mouth and intestine, and is associated with fatal complications that lead to a high impact on morbidity, mortality and the cost of cancer treatments. This reinforces that prevention of oral and intestinal mucositis is important to improve the success of chemotherapy. However, currently available treatments generally focus on treating symptoms, and little have been explored in preventing the development of the disease. Macrophages are abundant cells in the intestine, with the ability to respond to the microenvironment and change their polarization to different profiles, in an attempt to promote intestinal homeostasis. As macrophages are cells involved in the entire inflammatory response process and capable of acting in the intestinal microenvironment, we investigated whether reprogramming macrophages to different profiles in vitro could affect the clinical and histomorphological characteristics of murine intestinal mucositis caused by 5-fluorouracil (5 -FU). Treatment with different subpopulations of macrophages showed that macrophages not stimulated or stimulated for a regulatory profile were able to preserve the mucosal architecture, when evaluated histologically by the degree of inflammation, vascular changes, mucosal atrophy and presence of inflammatory cells; and also contributed to the preservation of goblet cells and the protection of mucus layer. Furthermore, administration of macrophages without stimuli also promoted body weight recovery in experimental animals.