Case Control Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2017; 23(22): 4039-4046
Published online Jun 14, 2017. doi: 10.3748/wjg.v23.i22.4039
Systemic interleukin-9 in inflammatory bowel disease: Association with mucosal healing in ulcerative colitis
Malgorzata Matusiewicz, Katarzyna Neubauer, Iwona Bednarz-Misa, Sabina Gorska, Malgorzata Krzystek-Korpacka
Malgorzata Matusiewicz, Iwona Bednarz-Misa, Malgorzata Krzystek-Korpacka, Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland
Katarzyna Neubauer, Department of Gastroenterology and Hepatology, Wroclaw Medical University, 50-556 Wroclaw, Poland
Sabina Gorska, Laboratory of Medical Microbiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland
Author contributions: Matusiewicz M and Krzystek-Korpacka M designed research; Neubauer K treated patients and collected material and clinical data from patients; Matusiewicz M, Bednarz-Misa I, Gorska S and Krzystek-Korpacka M performed the assays; Matusiewicz M and Krzystek-Korpacka M conducted statistical analyses; Matusiewicz M, Neubauer M and Krzystek-Korpacka M analysed and interpreted data; Matusiewicz M and Krzystek-Korpacka M wrote the paper; all authors critically revised the paper and approved its final version.
Supported by National Science Center, No. DEC-2011/01/D/NZ5/02835.
Institutional review board statement: The study protocol was approved by the Medical Ethics Committee of Wroclaw Medical University.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: We have no competing interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Malgorzata Krzystek-Korpacka, PhD, DSc (Med), Department of Medical Biochemistry, Wroclaw Medical University, ul. Chalubinskiego 10, 50-368 Wroclaw, Poland. malgorzata.krzystek-korpacka@umed.wroc.pl
Telephone: +48-71-7841395 Fax: + 48-71-7840085
Received: January 28, 2017
Peer-review started: February 5, 2017
First decision: February 23, 2017
Revised: March 28, 2017
Accepted: May 9, 2017
Article in press: May 9, 2017
Published online: June 14, 2017
Abstract
AIM

To evaluate circulating IL9 in inflammatory bowel disease and disease-associated anemia/cachexia and assess its potential as a mucosal healing marker.

METHODS

Serum IL9 as well as other cytokines (IL1β, IL6, IL13, IFNγ, TNFα, and VEGF-A) were determined in 293 individuals: 97 patients with Crohn’s disease (CD) and 74 with ulcerative colitis (UC) and in 122 apparently healthy controls. The clinical activity of CD and UC was expressed in terms of the Crohn’s Disease Activity Index (CDAI) and the Mayo Scoring System (MDAI), respectively, and the severity of bowel inflammation in UC patients was assessed using Mayo endoscopic score. Cytokine concentrations were measured by a flow cytometry-based method using Luminex xMAP® technology. High-sensitive C-reactive protein concentrations (hsCRP) were determined in CD and UC patients using the enhanced immunoturbidimetric method.

RESULTS

Systemic IL9 was significantly lower in healthy individuals [9 pg/mL (95%CI: 8.2-10)] than in patients with inflammatory bowel disease (IBD): both inactive [14.3 pg/mL (11.9-19.9)] and active [27.6 pg/mL (24.5-32), P < 0.0001]. Cytokine concentrations were significantly higher in active CD [27.4 pg/mL (23.4-32.2)] and in active UC [32.7 pg/mL (27-38.9)] compared to inactive diseases [15.9 pg/mL (10.8-23.4) in CD and 19.4 pg/mL (13.9-27.1) in UC, P = 0.001]. IL9 correlated weakly with CDAI (ρ = 0.32, P = 0.003) and MDAI (ρ = 0.35, P = 0.002) and strongly with endoscopic inflammation in UC (ρ = 0.74, P < 0.0001). As a negative marker of mucosal healing (MH), IL9 had an accuracy superior to hsCRP and IL6 [97% (P < 0.0001), 67% (P = 0.071), and 55% (P = 0.525), respectively]. IL9 was significantly higher in cachectic IBD patients [30.25 pg/mL (24.4-37.5) vs 21.88 pg/mL (18-26.5), P = 0.026] and negatively correlated with hemoglobin concentrations (ρ = -0.27, P < 0.001). Multiple regression showed IL1β and IL13 to be the independent predictors of circulating IL9 in healthy individuals, IFNγ or IL6 in active and inactive UC, respectively, and IL13 and VEGF-A in both active and inactive CD.

CONCLUSION

The systemic IL9 level is higher in IBD and corresponds with endoscopic inflammation, suggesting its possible application as a negative marker of mucosal healing in UC.

Keywords: Interleukin 9, Mucosal healing, Biomarker, Inflammatory bowel disease, Crohn’s disease, Ulcerative colitis, Cachexia, Anemia

Core tip: Based on a large cohort of patients, our results confirm elevation of IL9 in inflammatory bowel disease (IBD). Additionally, the data demonstrate associations between IL9 and both anemia and wasting syndromes accompanying IBD. Importantly, they show that an elevation in systemic IL9 in ulcerative colitis (UC) corresponds to mucosal inflammation, with IL9 displaying a high level of accuracy as a negative marker of mucosal healing. Also, our results demonstrate IL9 to be more tightly associated with proinflammatory and Th1 cytokines in UC and with angiogenic and Th2 cytokines in Crohn’s disease.