Interleukin-6 compared to the other Th17/Treg related cytokines in inflammatory bowel disease and colorectal cancer

World J Gastroenterol. 2020 Apr 28;26(16):1912-1925. doi: 10.3748/wjg.v26.i16.1912.

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

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Carcinogenesis / immunology*
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / prevention & control
  • Colorectal Neoplasms / surgery
  • Female
  • Forkhead Transcription Factors / metabolism
  • Gastrointestinal Agents / pharmacology
  • Gastrointestinal Agents / therapeutic use
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / pathology
  • Interleukin-6 / analysis
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / metabolism*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / surgery
  • Male
  • Middle Aged
  • Neoplasm Staging
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Transforming Growth Factor beta1 / analysis
  • Transforming Growth Factor beta1 / metabolism
  • Up-Regulation / immunology
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Gastrointestinal Agents
  • IL6 protein, human
  • Interleukin-6
  • TGFB1 protein, human
  • Transforming Growth Factor beta1