Therapeutic effects of vitamin D and IL-22 on methotrexate-induced mucositis in mice.
Animals
Disease Models, Animal
Drug Therapy, Combination
Gene Transfer Techniques
Inflammation Mediators
/ metabolism
Interleukins
/ administration & dosage
Intestinal Mucosa
/ drug effects
Methotrexate
/ pharmacology
Mice
Mice, Inbred BALB C
Mucositis
/ chemically induced
Vitamin D
/ administration & dosage
Weight Loss
/ drug effects
Interleukin-22
Journal
Anti-cancer drugs
ISSN: 1473-5741
Titre abrégé: Anticancer Drugs
Pays: England
ID NLM: 9100823
Informations de publication
Date de publication:
01 01 2022
01 01 2022
Historique:
pubmed:
5
8
2021
medline:
9
3
2022
entrez:
4
8
2021
Statut:
ppublish
Résumé
Mucositis is a common side effect of cancer therapies and transplant conditioning regimens. Management of mucositis involves multiple approaches from oral hygiene, anti-inflammatory, anti-apoptotic, cytoprotective, and antioxidant agents, to cryo-therapy, physical therapy, and growth factors. There is room for novel, affordable treatment options, or improvement of currently available therapies. Vitamin D has been shown to regulate mucosa-resident cell populations such as Th17 or innate lymphoid cells and critical mucosal cytokine IL-22; however, their therapeutic potential has not been put to test in preclinical mouse models. In this study, we aimed to test the therapeutic potential of vitamin D injections and IL-22 overexpression in a murine model of chemotherapy-induced mucositis. Balb/c mice were given daily intraperitoneal injections of vitamin D. Mucositis was induced by methotrexate. Another group received IL-22 plasmid via hydrodynamic gene delivery. Weight loss and intestinal histopathology, intestinal levels of cytokines IL-22, IL-17A, GM-CSF, IL-23, IFN-γ, TNF-α, and IL-10, and number of intestinal lamina propria B cell, neutrophil, and total innate lymphoid cells were quantified. Daily vitamin D injections ameliorated intestinal inflammation and elevated intestinal IL-22 levels compared with control groups. Temporal overexpression of IL-22 by hydrodynamic gene delivery slightly increased intestinal IL-22 but failed to confer significant protection from mucositis. To our knowledge, this is the first experimental demonstration in an animal model of mucositis of therapeutic use of vitamin D and IL-22 supplementation and our results with vitamin D suggest it may have merit in further trials in human mucositis patients.
Identifiants
pubmed: 34348356
doi: 10.1097/CAD.0000000000001128
pii: 00001813-202201000-00003
doi:
Substances chimiques
Inflammation Mediators
0
Interleukins
0
Vitamin D
1406-16-2
Methotrexate
YL5FZ2Y5U1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11-18Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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