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

Background & Aims: Crohn's disease (CD) is characterized by a marked accumu lation of activated Th1 type CD4(+) T cells and macrophages in inflamed int estinal mucosa. interleukin (IL)-18 is a recently described cytokine that m ainly exists in activated macrophages and shares biological activities with IL-12 in driving the development of Th1 type CD4(+) T cells by inducing in terferon gamma. To clarify the role of IL-18 in intestinal inflammation in CD, we assessed the functional role of IL-18 in regulating intestinal mucos al lymphocytes. Methods: Serum IL-18 concentration was measured by enzyme-l inked immunosorbent assay. Expression of IL-18 and IL-18 receptor in human intestinal mucosa was determined using immunohistochemistry and flow cytome try. The functional activity of 11-18 was assessed by the use of recombinan t 11-18 to stimulate both the growth of intestinal mucosal lymphocytes and IL-2 receptor induction activity. Results: The serum IL-18 concentration wa s significantly higher in patients with CD than normal controls. In the inf lamed colonic mucosa of CD, many IL-18(+)CD68(+) macrophages had infiltrate d the lamina propria. intestinal mucosal lymphocytes from CD expressed func tional 11-18 receptors. Recombinant IL-18 induced significant proliferative responses in freshly isolated mucosal lymphocytes from CD patients, but no t from normal controls. 11-18 up-regulated IL-2 receptor expression in muco sal lymphocytes from patients with CD, but not from normal controls. Conclu sions: These findings suggest that infiltrated macrophages in the inflamed intestinal mucosa in CD produce IL-18, and that macrophage-derived IL-18 ma y serve as a potent regulatory factor for intestinal mucosal lymphocytes, t hereby contributing to chronic intestinal inflammation in CD.