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

Gastroenterology. 2000 Dec;119(6):1514-23. doi: 10.1053/gast.2000.20260.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / physiology
  • Cell Membrane / metabolism
  • Crohn Disease / metabolism
  • Crohn Disease / pathology*
  • Humans
  • Interleukin-18 / metabolism
  • Interleukin-18 / physiology*
  • Interleukin-18 Receptor alpha Subunit
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology*
  • Lymphocytes / pathology*
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-18
  • Reference Values
  • Tissue Distribution


  • IL18R1 protein, human
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-18