Abstract
Ulcerative colitis is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental colitis was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Half of the mice received an i.v. dose of CT-1 (200 µg/kg) 2 h before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS administration. The severity of colitis was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF IFN-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before induction of colitis improves the clinical course, tissue damage, and inflammation in DSS-induced colitis in mice.
Highlights
Ulcerative colitis (UC) is a chronic, inflammatory bowel disease that disrupts colon structure and function
We show that CT-1 is able to partially prevent the development of dextran sulfate sodium (DSS)-induced experimental colitis in mice when administered before the insult, suggesting a potential additional prophylactic application
The fecal blood score increased progressively in the DSS group; whereas in the animals that received DSS + CT-1, it was lower at all time points
Summary
Ulcerative colitis (UC) is a chronic, inflammatory bowel disease that disrupts colon structure and function. UC affects mainly young patients and is characterized by alternation of acute and remission phases. UC is associated with a higher incidence of dysplasia and colorectal cancer, and can impact significantly the patients’ quality of life and working ability [1,2]. UC is most prevalent in northern Europe, especially in the United Kingdom and Scandinavia [3,4] and North America [5], whereas Asia is expected to reach highest incidence over the decade [6]. UC affects the colonic mucosa and submucosa with widespread superficial ulceration, destruction of epithelial architecture and integrity, crypt loss, submucosal edema, cellular infiltration, and intense inflammation [7]. The precise mechanisms are not yet fully understood, several mediators, including chemotactic peptides and pro-inflammatory cytokines are known to be involved [8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
