Helminth antigen-based strategy to ameliorate inflammation in an experimental model of colitis
Helminth antigen-based strategy to ameliorate inflammation in an experimental model of colitis
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DOI：
10.1111/j.1365-2249.2008.03805.x
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发表时间：
2009-01-01
影响因子：
4.6
通讯作者：
Khan, W. I.
中科院分区：
文献类型：
--
作者：
Motomura, Y.;Wang, H.;Khan, W. I.
炎症性肠病（IBD）是最常见和严重的肠道慢性炎症。在不同的辅助性T细胞（Th）亚群中，Th1型反应主要与克罗恩病（CD）相关，而蠕虫感染产生强烈的Th2型反应。IBD在发达国家最为普遍，但在蠕虫感染常见的国家却很少见。因此，人们假设蠕虫感染影响CD的发展，最近的临床和实验研究强烈表明蠕虫感染在IBD中的有益作用。在本研究中，我们检查了直肠粘膜下注射蠕虫抗原对随后的实验性结肠炎的影响。在二硝基苯磺酸（DNBS）诱导结肠炎前用旋毛虫抗原处理小鼠，DNBS诱导结肠炎后3 d处死小鼠，观察宏观、组织学、髓过氧化物酶（MPO）活性、诱导型一氧化氮合酶（iNOS）和细胞因子水平对结肠损伤的影响。根据宏观和组织学评估，既往螺旋体抗原治疗可显著降低结肠炎的严重程度，并降低死亡率。这种益处与结肠中MPO活性、白细胞介素(IL)-1 β生成和iNOS表达的下调以及IL-13和转化生长因子β生成的上调有关。这些结果清楚地表明，用寄生虫抗原局部治疗实验性结肠炎的有益作用，并迅速考虑以寄生虫抗原为基础治疗IBD，而不是用活寄生虫感染。
Inflammatory bowel disease (IBD) is the most common and serious chronic inflammatory condition of the gut. Among the distinct T helper (Th) cell subsets, a Th1 type response is associated predominantly with Crohn's disease (CD) while helminth infections generate a strong Th2 type response. IBD is most prevalent in developed countries but rare in countries where infections with helminths are common. Thus, it has been hypothesized that infection with helminth infection influence the development of CD and recent clinical and experimental studies suggest strongly a beneficial role of helminth infection in IBD. In the present study we examined the effects of rectal submucosal administration of helminth antigens on subsequent experimental colitis. Mice were treated with Trichinella spiralis antigens prior to the induction of dinitrobenzenesulphonic acid (DNBS)-induced colitis and were killed 3 days post-DNBS to assess colonic damage macroscopically, histologically and by myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOS) and cytokine levels. Previous treatment with T. spiralis antigens reduced the severity of colitis significantly, as assessed macroscopically and histologically, and reduced the mortality rate. This benefit was correlated with a down-regulation of MPO activity, interleukin (IL)-1 beta production and iNOS expression and an up-regulation of IL-13 and transforming growth factor-beta production in colon. These results clearly show a beneficial role of local treatment with helminth antigens for experimental colitis and prompt consideration of helminth antigen-based therapy for IBD instead of infection with live parasites.