Centre for Immunology and Infectious Disease, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK; Department of Internal Medicine, S. Matteo Hospital, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, University of Pavia, Pavia, Italy.
Eur J Immunol. 2014 Feb;44(2):370-85. doi: 10.1002/eji.201343524.
IL-13 has been implicated in the pathogenesis of ulcerative colitis (UC), and may have a role in animal models of gut fibrosis. We studied the involvement of IL-13 in inflammation and fibrosis in UC and Crohn's disease (CD). Intestinal biopsies and anti-CD3/CD28- or anti-CD2/CD28-stimulated lamina propria mononuclear cells from UC and CD patients and control subjects were cultured, and IL-13, IL-4, IL-5, IL-17A and IFN-γ production was measured. Mucosal IL-13-producing cells were characterised by flow cytometry. Gut explants from strictured CD, non-strictured CD and healthy donors were cultured ex vivo, and secreted IL-13, IL-1β and collagen were measured. IL-13 production by mucosal explants and activated lamina propria mononuclear cells did not differ between CD, UC and control subjects, and was at least a log lower than IFN-γ and IL-17A. IL-13-producing cells, and in particular natural killer T cells, were uniformly low in all groups. IL-4 and IL-5 were undetectable in culture supernatants. Explants of CD strictures produced low amounts of IL-13, whereas IL-1β and collagen were elevated. We could not confirm that UC or strictured CD are associated with elevated IL-13 production. These data suggest that an anti-IL-13 Ab would not be an appropriate therapeutic strategy in inflammatory bowel disease.
IL-13 已被牵连到溃疡性结肠炎 (UC) 的发病机制中,并且可能在肠道纤维化的动物模型中发挥作用。我们研究了 IL-13 在 UC 和克罗恩病 (CD) 中的炎症和纤维化中的作用。从 UC 和 CD 患者和对照受试者的肠活检和抗-CD3/CD28 或抗-CD2/CD28 刺激的固有层单核细胞中培养,并测量了 IL-13、IL-4、IL-5、IL-17A 和 IFN-γ 的产生。通过流式细胞术对粘膜产生 IL-13 的细胞进行了特征描述。从结构 CD、非结构 CD 和健康供体中培养了肠道外植体,并测量了分泌的 IL-13、IL-1β 和胶原蛋白。粘膜外植体和激活的固有层单核细胞产生的 IL-13 在 CD、UC 和对照组之间没有差异,并且至少比 IFN-γ 和 IL-17A 低一个对数级。所有组中产生 IL-13 的细胞,特别是自然杀伤 T 细胞,均均匀较低。培养上清液中未检测到 IL-4 和 IL-5。CD 狭窄处的外植体产生的 IL-13 量较低,而 IL-1β 和胶原蛋白升高。我们不能证实 UC 或结构 CD 与升高的 IL-13 产生有关。这些数据表明,抗 IL-13 Ab 可能不是炎症性肠病的合适治疗策略。