title: 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: Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
authors: Hisayuki
authors: H
authors: Matsunaga
authors: Ryota
authors: R
authors: Hokari
authors: Toshihide
authors: T
authors: Ueda
authors: Chie
authors: C
authors: Kurihara
authors: Hideaki
authors: H
authors: Hozumi
authors: Masaaki
authors: M
authors: Higashiyama
authors: Yoshikiyo
authors: Y
authors: Okada
authors: Chikako
authors: C
authors: Watanabe
authors: Shunsuke
authors: S
authors: Komoto
authors: Mitsuyasu
authors: M
authors: Nakamura
authors: Atsushi
authors: A
authors: Kawaguchi
authors: Shigeaki
authors: S
authors: Nagao
authors: Atsuo
authors: A
authors: Sekiyama
authors: Soichiro
authors: S
authors: Miura
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D003106:Colon / Q000378:metabolism*; D016264:Dextran Sulfate; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D053724:Receptors, Interleukin-18 / Q000096:biosynthesis; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000906:Antibodies; D020382:Interleukin-18; D016209:Interleukin-8; D012333:RNA, Messenger; D053724:Receptors, Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016264:Dextran Sulfate