Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
PLoS One. 2013;8(1):e54562. doi: 10.1371/journal.pone.0054562. Epub 2013 Jan 17.
Crohn's Disease (CD)-associated inflammation is supposed to be driven by T helper (Th)1/Th17 cell-derived cytokines, even though there is evidence that the mucosal profile of cytokine may vary with the evolution of the disease. We aimed at comparing the pattern of effector cytokines in early and established lesions of CD.
Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with (early lesions) or without post-operative recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (established lesions). Inflammatory cell infiltrate was examined by immunofluorescence and cytokine expression was analysed by real-time PCR, flow-cytometry and ELISA.
Before the appearance of endoscopic lesions, the mucosa of the neo-terminal ileum contained high number of T cells and macrophages, elevated levels of Th1-related cytokines and TNF-α and slightly increased IL-17A expression. Transition from this stage to endoscopic recurrence was marked by abundance of Th1 cytokines, marked increase in IL-17A, and induction of IL-6 and IL-23, two cytokines involved in the control of Th17 cell responses. In samples with established lesions, there was a mixed Th1/Th17 response with no TNF-α induction. Expression of IL-4 and IL-5 was up-regulated in both early and established lesions even though the fraction of IL-4-producing cells was lower than that of cells producing either interferon-γ or IL-17A.
Distinct mucosal profiles of cytokines are produced during the different phases of CD. A better understanding of the cytokines temporally regulated in CD tissue could help optimize therapeutic interventions in CD.
克罗恩病（CD）相关炎症被认为是由辅助性 T 细胞（Th）1/Th17 细胞衍生的细胞因子驱动的，尽管有证据表明黏膜细胞因子的特征可能随疾病的进展而变化。我们旨在比较 CD 的早期和已建立病变中效应细胞因子的模式。
从接受回肠结肠切除术的 CD 患者的新末端回肠中采集黏膜样本，伴有（早期病变）或不伴有术后复发，以及患有长期疾病的 CD 患者的末端回肠行肠切除术（已建立病变）。通过免疫荧光检查炎症细胞浸润，通过实时 PCR、流式细胞术和 ELISA 分析细胞因子表达。
在出现内镜病变之前，新末端回肠的黏膜含有大量 T 细胞和巨噬细胞，Th1 相关细胞因子和 TNF-α水平升高，IL-17A 表达略有增加。从这个阶段到内镜复发的转变以 Th1 细胞因子丰富为特征，IL-17A 显著增加，并诱导 IL-6 和 IL-23，这两种细胞因子参与控制 Th17 细胞反应。在已建立病变的样本中，存在混合的 Th1/Th17 反应，没有 TNF-α诱导。IL-4 和 IL-5 的表达在早期和已建立的病变中均上调，尽管产生 IL-4 的细胞比例低于产生干扰素-γ或 IL-17A 的细胞比例。
在 CD 的不同阶段产生了不同的细胞因子黏膜谱。更好地了解 CD 组织中随时间调节的细胞因子可能有助于优化 CD 的治疗干预。
