Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2015; 21(28): 8580-8587
Published online Jul 28, 2015. doi: 10.3748/wjg.v21.i28.8580
Restraint stress induces and exacerbates intestinal inflammation in interleukin-10 deficient mice
Seong-Joon Koh, Ji Won Kim, Byeong Gwan Kim, Kook Lae Lee, Joo Sung Kim
Seong-Joon Koh, Ji Won Kim, Byeong Gwan Kim, Kook Lae Lee, Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul 110-744, South Korea
Joo Sung Kim, Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-744, South Korea
Author contributions: Koh SJ collected the data and wrote the manuscript; Kim JS was in charge of this study; Kim JW, Kim BG and Lee KL contributed to the data acquisition and reviewed the manuscript; all authors have read and approved the final version of the manuscript.
Supported by SNUH Research Fund, No. 06-2011-1770; and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, No. NRF-2014R1A1A2057695.
Institutional review board statement: This study is not a human subject study. Therefore, this study was not reviewed and approved by Institutional Review Board of Seoul National University Hospital.
Institutional animal care and use committee statement: All animal procedures and stress protocols were approved by the Institutional Animal Care and Use Committee of Seoul National University Hospital.
Conflict-of-interest statement: None of the authors had conflicts of interest that potentially influence the described research, and there was no external financial support.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at jooskim@snu.ac.kr.
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: Joo Sung Kim, MD, PhD, Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-744, South Korea. jooskim@snu.ac.kr
Telephone: +82-2-7408112 Fax: +82-2-7436701
Received: January 24, 2015
Peer-review started: January 25, 2015
First decision: February 10, 2015
Revised: March 30, 2015
Accepted: April 9, 2015
Article in press: April 9, 2015
Published online: July 28, 2015
Processing time: 186 Days and 20.5 Hours
Abstract

AIM: To investigate the effects of restraint stress on chronic colitis in interleukin (IL)-10 deficient (IL-10-/-) mice.

METHODS: The first experiment compared the effect of restraint stress on the development of intestinal inflammation in wild-type and IL-10-/- mice. Both wild-type and IL-10-/- mice were physically restrained in a well-ventilated, 50 cm3 conical polypropylene tube for 2 h per day for three consecutive days. The second experiment was performed to assess the effect of restraint stress on exacerbation of colitis induced by piroxicam in IL-10-/- mice. The IL-10-/- mice were exposed to restraint stress for 2 h per day for 3 consecutive days, and then treated with piroxicam for 4 d at a dose of 200 ppm administered in the rodent chow.

RESULTS: In the first experiment, none of the wild-type mice with or without restraint stress showed clinical and histopathological abnormality in the gut. However, IL-10-/- mice exposed to restraint stress exhibited histologically significant intestinal inflammation as compared to those without restraint stress. In the second experiment, restraint stress significantly reduced body weight and increased the severity of intestinal inflammation assessed by histopathologic grading in IL-10-/- mice. Colonic IL12p40 mRNA expression was strongly increased in mice exposed to restraint stress.

CONCLUSION: This novel animal model could be useful in future study of psychological stress in the pathogenesis of inflammatory bowel disease.

Keywords: Stress; Colitis; Interleukin-10; Inflammatory bowel disease; Mouse model

Core tip: We investigated the effect of restraint stress on the development and worsening of bowel inflammation in interleukin (IL)-10-/- mice and developed a novel animal model. This is the first study to demonstrate the effect of restrain stress in inducing and exacerbating chronic colitis in IL-10-/- mice. We believe that this novel animal model could be useful in future study of psychological stress in the pathogenesis of inflammatory bowel disease because this model develops chronic colitis due to interaction of genetic, immune dysregulation, microbial environment, and stress factor.