Interleukin-18 overproduction exacerbates the development of colitis with markedly infiltrated macrophages in interleukin-18 transgenic mice

Takahiro Ishikura, Takanori Kanai, Koji Uraushihara, Ryoichi Iiyama, Shin Makita, Teruji Totsuka, Motomi Yamazaki, Taisuke Sawada, Tetsuya Nakamura, Tatsuya Miyata, Tetsuji Kitahora, Toshifumi Hibi, Tomoaki Hoshino, Mamoru Watanabe

研究成果: Article査読

55 被引用数 (Scopus)

抄録

Background and Aim: The authors have previously shown that production of interleukin (IL)-18 was increased in the inflamed mucosa of patients with Crohn's disease (CD) and blockade of IL-18 ameliorated the murine model of CD. This demonstrated that IL-18 plays a significant role during intestinal inflammation. However, the initial role of IL-18 during intestinal inflammation was unclear; therefore the susceptibility of IL-18 transgenic (Tg) mice to acute dextran sulfate sodium (DSS)-induced colitis was examined. Methods: Interleukin-18 Tg and wild-type (WT) mice were fed 2.0% of DSS for 8 days. The total clinical scores (bodyweight loss, stool consistency, and rectal bleeding), colon length and histological scores were assessed. The expressions of surface markers and IL-18 on infiltrating lamina propria mononuclear cells were analyzed immunohistochemistrically. Mesenteric lymph node (MLN) cells were isolated and the expressions of CD4+ T-cell activation markers (CD69, CD25 and IL18R) were analyzed by flow cytometry. Results: The IL-18 Tg mice exhibited an increased susceptibility to DSS-induced colitis, as shown by significantly increased clinical, histological scores, and more severe colonic shortening compared with WT mice. Immunohistochemical analysis revealed a significant increase of IL-18 production and CD11b+ macrophages but not CD4+T cells in the inflamed mucosa in DSS-fed IL-18 Tg compared with DSS-fed WT mice. Furthermore, MLN cells revealed no evidence of increased CD4+T-cell activation in DSS-fed IL-18 Tg. Conclusions: These findings suggest that IL-18 overproduction in the mucosa plays an important role in the marked infiltration of macrophages and exacerbates colitis in IL-18 Tg mice.

本文言語English
ページ(範囲)960-969
ページ数10
ジャーナルJournal of Gastroenterology and Hepatology (Australia)
18
8
DOI
出版ステータスPublished - 2003 8月 1
外部発表はい

ASJC Scopus subject areas

  • 肝臓学
  • 消化器病学

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