Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2020; 26(16): 1912-1925
Published online Apr 28, 2020. doi: 10.3748/wjg.v26.i16.1912
Interleukin-6 compared to the other Th17/Treg related cytokines in inflammatory bowel disease and colorectal cancer
Tsvetelina Veselinova Velikova, Lyuba Miteva, Noyko Stanilov, Zoya Spassova, Spaska Angelova Stanilova
Tsvetelina Veselinova Velikova, Clinical Immunology, University Hospital “Lozenetz”, Sofia 1407, Bulgaria
Lyuba Miteva, Spaska Angelova Stanilova, Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Stara Zagora 6000, Bulgaria
Noyko Stanilov, Oncoplastic Unit, University College London Hospital, London 235, United Kingdom
Zoya Spassova, Clinic of Gastroenterology, University Hospital “St. Ivan Rilski”, Sofia 1431, Bulgaria
Author contributions: Velikova TV was involved in the conceptualization, data curation, funding acquisition, investigation, project administration, writing-original draft; Miteva L performed the data curation, formal analysis, investigation, methodology, software, visualization, writing review and editing; Stanilov N was involved in the data curation, investigation, resources, writing review and editing; Spassova Z took part in the resources, supervision, writing review and editing; Stanilova SA performed the conceptualization, funding acquisition, investigation, methodology, project administration, supervision, validation, visualization, writing review and editing.
Supported by the Medical University of Sofia, No. 22. 2012-2013; and Trakia University of Stara Zagora, No. 1. 2016 and No. 2. 2017.
Institutional review board statement: The study was reviewed and approved by the Medical University of Sofia Institutional Review Board (the Ethical Committee).
Conflict-of-interest statement: The authors declare that there is no conflict of interest regarding the publication of this article.
Data sharing statement: Consent from the patients for data sharing was obtained, and additionally, the presented data are anonymized, and the risk of identification is low. No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Tsvetelina Veselinova Velikova, MD, PhD, Assistant professor, Clinical Immunology, University Hospital Lozenetz, Kozyak 1 Street, Sofia 1407, Bulgaria. tsvelikova@medfac.mu-sofia.bg
Received: December 25, 2019
Peer-review started: December 25, 2019
First decision: January 19, 2020
Revised: January 24, 2020
Accepted: April 4, 2020
Article in press: April 4, 2020
Published online: April 28, 2020
Processing time: 124 Days and 17.8 Hours
Abstract
BACKGROUND

The connection between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is well-established, as persistent intestinal inflammation plays a substantial role in both disorders. Cytokines may further influence the inflammation and the carcinogenesis process.

AIM

To compare cytokine patterns of active IBD patients with early and advanced CRC.

METHODS

Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior, in colon specimens, as mRNA biomarkers, and their serum protein levels.

RESULTS

We found a significant difference between higher gene expression of FoxP3, TGFb1, IL-10, and IL-23, and approximately equal level of IL-6 in CRC patients in comparison with IBD patients. After stratification of CRC patients, we found a significant difference in FoxP3, IL-10, IL-23, and IL-17A mRNA in early cases compared to IBD, and IL-23 alone in advanced CRC. The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.

CONCLUSION

Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes (TGFb1, IL-10, IL-23, and transcription factor FoxP3) is a crucial primarily for CRC development. The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.

Keywords: Inflammatory bowel disease; Colorectal cancer; Cytokines; mRNA; Interleukin-6; Th17/Treg cells

Core tip: In our paper, we showed that IL-6 upregulation is essential for both inflammatory bowel disease and colorectal cancer (CRC) development, whereas the upregulation of other Th17/Treg related genes (TGFb1, IL-10, IL-23, and transcription factor FoxP3) is a crucial primarily for CRC development. The significantly upregulated IL-6 could be a potential drug target for inflammatory bowel disease and prevention of CRC development as well.