Role of regulatory T cells in irinotecan-induced intestinal mucositis.

Autor: Fernandes C; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil. Electronic address: camilafarmaco@gmail.com., Wanderley CWS; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil., Silva CMS; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil., Muniz HA; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil., Teixeira MA; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil., Souza NRP; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil., Cândido AGF; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil., Falcão RB; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil., Souza MHLP; Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Brazil., Almeida PRC; Department of Pathology and Forensic Medicine, Faculty of Medicine, Federal University of Ceará, Brazil., Câmara LMC; Department of Pathology and Forensic Medicine, Faculty of Medicine, Federal University of Ceará, Brazil., Lima-Júnior RCP; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil. Electronic address: robertocesar@ufc.br.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2018 Mar 30; Vol. 115, pp. 158-166. Date of Electronic Publication: 2018 Jan 04.
DOI: 10.1016/j.ejps.2018.01.006
Abstrakt: Intestinal mucositis (IM) is a common side effect of irinotecan-based chemotherapy. The involvement of inflammatory mediators, such as TNF-α, IL1-β, IL-18 and IL-33, has been demonstrated. However, the role of adaptive immune system cells, whose activation is partially regulated by these cytokines, is yet unknown. Thus, we investigated the role of regulatory T cells (Tregs) in irinotecan-induced IM. C57BL/6 mice were injected with saline or irinotecan (75mgkg -1 , i.p.), once a day for 4days, and euthanized at day 1, 3, 5 or 7 following the first dose of irinotecan. For Treg depletion, the mice were pretreated with a low single dose of cyclophosphamide (100mgkg -1 , i.p). Intestinal lamina propria lymphocytes were harvested and purified by Percoll gradient. Treg and Th17 cells were identified by flow cytometry. Blood leukocyte count was obtained and ileum samples were collected for histopathological analysis and myeloperoxidase assay. IM caused an accumulation of Tregs and Th17 cells over time. Treg depletion exacerbated intestinal damage, diarrhea, neutrophil infiltration and animal mortality, despite a reduction in Th17 cell number. The frequency of other Th cells increased and was positively correlated with neutrophil infiltration. Tregs showed a negative correlation with neutrophils and the frequency of non-regulatory Th cells. In conclusion, Tregs are important in the control of intestinal damage induced by irinotecan, and their depletion showed a deleterious effect on IM. Activation of these cells appears to be a compensatory mechanism for intestinal inflammation.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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