Takagi H, Kanai T, Okazawa A, Kishi Y, Sato T, Takaishi H, Inoue N, Ogata H, Iwao Y, Hoshino K, Takeda K, Akira S, Watanabe M, Ishii H, Hibi T
Dept. of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Scand J Gastroenterol. 2003 Aug;38(8):837-44. doi: 10.1080/00365520310004047.
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.
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.
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.
These results suggest that IL-18 might function with manners different from IL-12 at some pathological conditions in the development of colitis.
白细胞介素（IL）-12和IL-18是主要的相互协作的干扰素（IFN）-γ诱导因子。本研究旨在确定IL-12和IL-18在小鼠葡聚糖硫酸钠（DSS）结肠炎发展过程中的不同作用。
用DSS诱导IL-12p35基因敲除（-/-）、IL-18基因敲除（-/-）、IL-18受体基因敲除（-/-）小鼠及对照小鼠患结肠炎。采用存活率、体重减轻评分、腹泻评分、便血评分和组织学评分进行临床和组织病理学分析。此外，使用特异性酶联免疫测定法检测固有层单核细胞（LPMC）产生的细胞因子。
IL-12p35基因敲除小鼠仅发生轻度疾病，无致死性且组织病理学异常较少。相比之下，与对照小鼠相比，IL-18基因敲除和IL-18受体基因敲除小鼠发生更严重的结肠炎，伴有高致死率和更多组织病理学异常。与对照小鼠相比，喂食DSS的IL-18基因敲除小鼠的LPMC产生的IFN-γ量显著更高，而喂食DSS的IL-12基因敲除小鼠的LPMC产生的IFN-γ和肿瘤坏死因子（TNF）-α量更低。
这些结果表明，在结肠炎发展的某些病理条件下，IL-18可能以与IL-12不同的方式发挥作用。
