Physiological stress exacerbates murine colitis by enhancing proinflammatory cytokine expression that is dependent on IL-18.

Abstract

Psychological stress is an environmental factor considered to be a precipitating factor of inflammatory bowel disease. Interleukin (IL)-18 plays a role in stress-induced aggravation in some diseases. The aim of this study was to establish a model of murine colitis exacerbated by psychological stress and to clarify the role of IL-18 in this model. Male C57Bl/6 mice and IL-18(-/-) mice were used for this study. The mice received dextran sulfate sodium (DSS) for induction of colitis. Some mice were exposed to psychological stress using a communication box. Body weight, colonic length, and histological inflammation were measured for assessment of colitis. Tumor necrosis factor (TNF)-α and IL-18 expression in the colon and IL-18 expression in the adrenal gland were analyzed using real-time PCR. The effect of anti-IL-18 antibody was also investigated. Effects of TNF-α and IL-18 on cytokine expressions were studied using the colonic epithelial cell line LS174T. Induction of psychological stress in DSS-treated wild-type mice significantly exacerbated colitis with enhanced expression of proinflammatory cytokines and IL-18. However, induction of psychological stress in DSS-treated IL-18(-/-) mice did not aggravate colitis compared with that in the IL-18(-/-) group given only DSS treatment. Stress-induced aggravation of colitis was ameliorated significantly by anti-IL-18 antibody treatment. IL-18 did not enhance TNF-α-induced expression of intercellular adhesion molecule-1 or IL-8 in LS174T. We established a model of colitis exacerbated by psychological stress. Psychological stress enhanced IL-18 expression and plays a proinflammatory role in stress-induced aggravation of colitis.

• Authors: Hisayuki Matsunaga, Ryota Hokari, Toshihide Ueda, Chie Kurihara, Hideaki Hozumi, Masaaki Higashiyama, Yoshikiyo Okada, Chikako Watanabe, Shunsuke Komoto, Mitsuyasu Nakamura, Atsushi Kawaguchi, Shigeaki Nagao, Atsuo Sekiyama, Soichiro Miura
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 301 Issue 3 Pg. G555-64 (Sep 2011) ISSN: 1522-1547 [Electronic] United States
• PMID: 21719737 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Interleukin-18
• Interleukin-8
• RNA, Messenger
• Receptors, Interleukin-18
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• Dextran Sulfate

Topics

• Adrenal Glands (metabolism)
• Animals
• Antibodies (pharmacology)
• Colitis (chemically induced, pathology)
• Colon (metabolism)
• Dextran Sulfate
• Intercellular Adhesion Molecule-1 (biosynthesis)
• Interleukin-18 (biosynthesis, immunology)
• Interleukin-8 (biosynthesis)
• Male
• Mice
• Mice, Inbred C57BL
• RNA, Messenger (metabolism)
• Receptors, Interleukin-18 (biosynthesis)
• Stress, Psychological (pathology, physiopathology)
• Tumor Necrosis Factor-alpha