Arai F, Takahashi T, Furukawa K, Matsushima K, Asakura H
Third Department of Internal Medicine, Niigata University School of Medicine, Japan.
Dig Dis Sci. 1998 Sep;43(9):2071-9. doi: 10.1023/a:1018815432504.
To elucidate the possible role of proinflammatory cytokines in inflammatory bowel disease, the expression and localization of interleukin (IL) -6 and IL-8 mRNAs were examined in colonic biopsy specimens obtained from 10 patients with active ulcerative colitis (UC), 5 with inactive UC, 6 with Crohn's disease (CD), and 5 normal controls. In situ hybridization with digoxigenin-labeled probes and immunohistochemistry for both cytokines were performed. The IL-6 mRNA expression was enhanced in the inflamed mucosa in 4 of 6 CD patients, while that of UC patients stayed at baseline. In contrast, IL-8 mRNA expression was apparently augmented (P = 0.044) in 7 of 10 active UC and 3 of 6 CD patients (NS). The cell count positive for IL-8 mRNA per unit area was definitely increased in moderate/severe UC when compared to mild UC (53.1 +/- 14.4/mm2 vs 9.0 +/- 5.1/mm2, P = 0.028) according to the degree of inflammation. IL-6 mRNA positive cells in CD were preferentially located in deeper lamina propria than IL-8 mRNA positive cells in UC. Interestingly, IL-8 mRNA was expressed in the mucosal epithelial cells in one UC patient. The patients treated by corticosteroids tended to show suppressed expression of each mRNA, except one patient with intractable UC. Our data suggest enhanced expression of mucosal IL-6 mRNA in CD and of IL-8 mRNA in UC by infiltrating mononuclear cells, indicating the distinct participation of each cytokine in the pathogenesis of UC and CD. Moreover, intestinal epithelial cells in UC occasionally exhibit IL-8 mRNA.
为阐明促炎细胞因子在炎症性肠病中的可能作用,我们检测了10例活动期溃疡性结肠炎(UC)患者、5例非活动期UC患者、6例克罗恩病(CD)患者及5例正常对照者结肠活检标本中白细胞介素(IL)-6和IL-8 mRNA的表达及定位。采用地高辛标记探针进行原位杂交,并对两种细胞因子进行免疫组化检测。6例CD患者中有4例炎症黏膜中IL-6 mRNA表达增强,而UC患者的该表达维持在基线水平。相反,10例活动期UC患者中的7例及6例CD患者中的3例IL-8 mRNA表达明显增加(P = 0.044)(无统计学差异)。根据炎症程度,中度/重度UC每单位面积IL-8 mRNA阳性细胞计数明显高于轻度UC(53.1±14.4/mm²对9.0±5.1/mm²,P = 0.028)。CD中IL-6 mRNA阳性细胞比UC中IL-8 mRNA阳性细胞更倾向于位于固有层深部。有趣的是,1例UC患者的黏膜上皮细胞中有IL-8 mRNA表达。除1例难治性UC患者外,接受皮质类固醇治疗的患者各mRNA表达往往受到抑制。我们的数据表明,CD中黏膜IL-6 mRNA及UC中IL-8 mRNA因单核细胞浸润而表达增强,提示每种细胞因子在UC和CD发病机制中发挥不同作用。此外,UC中的肠上皮细胞偶尔会出现IL-8 mRNA。