Dieleman L A, Palmen M J, Akol H, Bloemena E, Peña A S, Meuwissen S G, Van Rees E P
Departments of Gastroenterology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
Clin Exp Immunol. 1998 Dec;114(3):385-91. doi: 10.1046/j.1365-2249.1998.00728.x.
Oral administration of DSS has been reported to induce an acute and chronic colitis in mice. The aim of our study was to evaluate if the chronic phase of DSS-induced colitis was characterized by a Th1/Th2 response and how this would relate to mucosal regeneration. Swiss Webster mice were fed 5% DSS in their drinking water for 7 days, followed by 2-5 weeks consumption of water. Control mice received only water. The animals were killed at 3 and 6 weeks after induction. Their colons were isolated for histology and immunohistochemistry, using specific MoAbs for T and B cells, macrophages, interferon-gamma (IFN-gamma), IL-4 and IL-5. Colons were scored for inflammation, damage and regeneration. Two weeks after stopping DSS the colonic epithelium had only partially healed. Total colitis scores were still increased, especially in the distal colon, which was due to more inflammation, damage and less regeneration. In areas of incomplete colonic healing the basal parts of the lamina propria contained macrophages and CD4+ T cells. These CD4+ T cells showed a focal increase of IFN-gamma and IL-4 staining compared with control animals. These findings were still observed 5 weeks after stopping DSS in some mice, albeit less extensive. Chronic DSS-induced colitis is characterized by focal epithelial regeneration and a Th1 as well as Th2 cytokine profile. We postulate that chronic immune activation mediated by both populations of Th cells can interfere with colonic healing and can play a role in the pathogenesis of chronic colitis.
据报道,口服葡聚糖硫酸钠(DSS)可诱导小鼠发生急性和慢性结肠炎。我们研究的目的是评估DSS诱导的结肠炎慢性期是否以Th1/Th2反应为特征,以及这与黏膜再生有何关系。给瑞士 Webster 小鼠饮用含5% DSS的水7天,随后饮用2 - 5周的普通水。对照小鼠只饮用普通水。在诱导后3周和6周处死动物。分离它们的结肠用于组织学和免疫组织化学检查,使用针对T细胞、B细胞、巨噬细胞、干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)和白细胞介素-5的特异性单克隆抗体。对结肠的炎症、损伤和再生情况进行评分。停止给予DSS两周后,结肠上皮仅部分愈合。全结肠炎评分仍升高,尤其是在远端结肠,这是由于炎症和损伤更严重,再生较少。在结肠愈合不完全的区域,固有层基部含有巨噬细胞和CD4 + T细胞。与对照动物相比,这些CD4 + T细胞的IFN-γ和IL-4染色呈局灶性增加。在一些小鼠中,停止给予DSS 5周后仍可观察到这些发现,尽管程度较轻。慢性DSS诱导的结肠炎的特征是局灶性上皮再生以及Th1和Th2细胞因子谱。我们推测,由这两种Th细胞群体介导的慢性免疫激活可干扰结肠愈合,并在慢性结肠炎的发病机制中起作用。