Interleukin 18 is a potent proliferative factor for intestinal mucosal lymphocytes in Crohn's disease

Takanori Kanai, Mamoru Watanabe, Akira Okazawa, Koichi Nakamaru, Makiyo Okamoto, Makoto Naganuma, Hiromasa Ishii, Masao Ikeda, Masashi Kurimoto, Toshifumi Hibi

Research output: Contribution to journalArticlepeer-review

122 Citations (Scopus)


Background & Aims: Crohn's disease (CD) is characterized by a marked accumulation of activated Th1 type CD4+ T cells and macrophages in inflamed intestinal mucosa. Interleukin (IL)-18 is a recently described cytokine that mainly exists in activated macrophages and shares biological activities with IL-12 in driving the development of Th1 type CD4+ T cells by inducing interferon gamma. To clarify the role of IL-18 in intestinal inflammation in CD, we assessed the functional role of IL-18 in regulating intestinal mucosal lymphocytes. Methods: Serum IL-18 concentration was measured by enzyme-linked immunosorbent assay. Expression of IL-18 and IL-18 receptor in human intestinal mucosa was determined using immunohistochemistry and flow cytometry. The functional activity of IL-18 was assessed by the use of recombinant IL-18 to stimulate both the growth of intestinal mucosal lymphocytes and IL-2 receptor induction activity. Results: The serum IL-18 concentration was significantly higher in patients with CD than normal controls. In the inflamed colonic mucosa of CD, many IL-18+CD68+ macrophages had infiltrated the lamina propria. Intestinal mucosal lymphocytes from CD expressed functional IL-18 receptors. Recombinant IL-18 induced significant proliferative responses in freshly isolated mucosal lymphocytes from CD patients, but not from normal controls. 1L-18 up-regulated IL-2 receptor expression in mucosal lymphocytes from patients with CD, but not from normal controls. Conclusions: These findings suggest that infiltrated macrophages in the inflamed intestinal mucosa in CD produce IL-18, and that macrophage-derived IL-18 may serve as a potent regulatory factor for intestinal mucosal lymphocytes, thereby contributing to chronic intestinal inflammation in CD.

Original languageEnglish
Pages (from-to)1514-1523
Number of pages10
Issue number6
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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