Lopes Ana I, Quiding-Jarbrink Marianne, Palha Ana, Ruivo José, Monteiro Lurdes, Oleastro Mónica, Santos Andrea, Fernandes Afonso
Gastroenterology Unit, Paediatric Department, University Hospital Santa Maria, Lisboa, Portugal.
Clin Diagn Lab Immunol. 2005 Aug;12(8):994-1002. doi: 10.1128/CDLI.12.8.994-1002.2005.
Helicobacter pylori infection is one of the most common gastrointestinal infections worldwide and almost invariably causes chronic gastritis in the infected host. A predominant Th1 profile has been demonstrated in H. pylori-infected mucosa from adults, but no previous study has evaluated in situ cytokine expression in children. We therefore examined expression of proinflammatory, anti-inflammatory, and regulatory cytokines by immunohistochemistry in cryopreserved antral biopsy specimens from 10 H. pylori-infected and 10 uninfected children and correlated expression of cytokines with histology scores. Concomitant expression of interleukin-8 (IL-8), gamma interferon (IFN-gamma), IL-4, transforming growth factor beta, and tumor necrosis factor alpha was seen in 8/10 H. pylori-infected cases and in 5/10 noninfected cases; all H. pylori-infected subjects showed staining for at least two of the cytokines. The proportion of epithelial cytokine-specific staining did not differ significantly between the groups, either in surface or glandular epithelium. Furthermore, no significant differences were noticed between intraepithelial or lamina propria lymphocyte staining in the groups. There was, however, a tendency of higher numbers of IFN-gamma- and IL-8-positive cells in the H. pylori-infected group. IFN-gamma and IL-8 lamina propria lymphocyte expression correlated significantly with antrum chronic inflammation, but there was no correlation between histology scores and epithelial cytokine expression. When the same techniques were used, the cytokine response appeared to be smaller in H. pylori-infected children than in adults, and there was no clear Th1 dominance. These results therefore suggest a different mucosal immunopathology in children. It remains to be determined whether the gastric immune response is downregulated in children with H. pylori infection and whether this is relevant to the outcome of infection.
幽门螺杆菌感染是全球最常见的胃肠道感染之一,几乎总是会在受感染宿主中引发慢性胃炎。在成人幽门螺杆菌感染的黏膜中已证实存在主要的Th1型免疫反应,但此前尚无研究评估儿童原位细胞因子的表达情况。因此,我们通过免疫组织化学方法检测了10名幽门螺杆菌感染儿童和10名未感染儿童的冷冻胃窦活检标本中促炎、抗炎和调节性细胞因子的表达,并将细胞因子表达与组织学评分进行关联分析。在10例幽门螺杆菌感染病例中的8例以及10例未感染病例中的5例中,同时观察到白细胞介素-8(IL-8)、γ干扰素(IFN-γ)、IL-4、转化生长因子β和肿瘤坏死因子α的表达;所有幽门螺杆菌感染的受试者至少有两种细胞因子呈阳性染色。两组在表面上皮或腺上皮中,上皮细胞因子特异性染色的比例无显著差异。此外,两组在固有层或上皮内淋巴细胞染色方面也未发现显著差异。然而,幽门螺杆菌感染组中IFN-γ和IL-8阳性细胞数量有增多的趋势。IFN-γ和IL-8在固有层淋巴细胞中的表达与胃窦慢性炎症显著相关,但组织学评分与上皮细胞因子表达之间无相关性。当采用相同技术时,幽门螺杆菌感染儿童的细胞因子反应似乎比成人小,且没有明显的Th1优势。因此,这些结果提示儿童存在不同的黏膜免疫病理学特征。幽门螺杆菌感染儿童的胃免疫反应是否下调以及这是否与感染结局相关,仍有待确定。