Interleukin 18 is a potent proliferative factor for intestinal mucosal lymphocytes in Crohn's disease
T Kanai, M Watanabe, A Okazawa, K Nakamaru… - Gastroenterology, 2000 - Elsevier
T Kanai, M Watanabe, A Okazawa, K Nakamaru, M Okamoto, M Naganuma, H Ishii, M Ikeda…
Gastroenterology, 2000•ElsevierBackground & 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 …
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 …
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. IL-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.
Elsevier