Contrasting action of IL-12 and IL-18 in the development of dextran sodium sulphate colitis in mice.
BACKGROUND
Interleukin (IL)-12 and IL-18 are major interferon (IFN)-gamma-inducing factors that collaborate with each other. The present study was conducted to determine the distinct roles of IL-12 and IL-18 in the development of dextran sulphate sodium (DSS) colitis in mice.


METHODS
Colitis was induced in IL-12p35(-/-), IL-18(-/-), IL-18 receptor(-/-) and control mice with DSS. Clinical and histopathological analysis was conducted using survival rate, weight loss score, diarrhoea score, bloody stool score and histological score. In addition, cytokine production by lamina propria mononuclear cells (LPMCs) was examined using the specific enzyme-linked immunoassay.


RESULTS
IL-12p35(-/-) mice developed only a mild disease associated with no lethality and few histopathological abnormalities. In contrast, IL-18(-/-) and IL-18R(-/-) mice developed more severe colitis associated with high lethality and more histopathological abnormalities compared with control mice. LPMCs from DSS-fed IL-18(-/-) mice produced significantly higher amounts of IFN-gamma, while LPMCs from DSS-fed IL-12(-/-) mice produced lower amounts of IFN-gamma and tumour necrosis factor (TNF)-alpha compared with control mice.


CONCLUSIONS
These results suggest that IL-18 might function with manners different from IL-12 at some pathological conditions in the development of colitis.
Takagi
H
H
Dept. of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Kanai
T
T
Okazawa
A
A
Kishi
Y
Y
Sato
T
T
Takaishi
H
H
Inoue
N
N
Ogata
H
H
Iwao
Y
Y
Hoshino
K
K
Takeda
K
K
Akira
S
S
Watanabe
M
M
Ishii
H
H
Hibi
T
T
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism; D016264:Dextran Sulfate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000502:physiology*; D020382:Interleukin-18 / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D016264:Dextran Sulfate