Interleukin 18 is a potent proliferative factor for intestinal mucosal lymphocytes in Crohn's disease.
OBJECTIVE
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.
Kanai
T
T
Keio Cancer Center, Tokyo, Japan.
Watanabe
M
M
Okazawa
A
A
Nakamaru
K
K
Okamoto
M
M
Naganuma
M
M
Ishii
H
H
Ikeda
M
M
Kurimoto
M
M
Hibi
T
T
D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020382:Interleukin-18 / Q000378:metabolism / Q000502:physiology*; D053727:Interleukin-18 Receptor alpha Subunit; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology*; D018123:Receptors, Interleukin / Q000378:metabolism; D053724:Receptors, Interleukin-18; D012016:Reference Values; D014018:Tissue Distribution
C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18