Laboratory of Gastroenterology, Institute of Clinical Medicine, University of Tromsø, and Department of Medical Gastroenterology, University Hospital of Northern Norway, 9037 Tromsø, Norway.
Cytokine. 2011 Dec;56(3):633-40. doi: 10.1016/j.cyto.2011.08.036. Epub 2011 Sep 25.
Crohn's disease (CD) and ulcerative colitis (UC) have been associated with a T helper1 (TH1) and a TH2 cytokine profile, respectively. Recently, a TH17 lineage has been introduced, but their role in the inflammation of CD and UC is not fully understood.
To characterize the cytokines directing the TH17 cells and their interactions with TH1 cells in the mucosa of untreated patients with CD and UC.
Seventy-nine patients with untreated UC, 32 patients with untreated CD and 23 controls with no signs of colon disease were included in the study. Clinical indices for ulcerative colitis (UCDAI) and Crohn's disease (CDAI) were assessed. Biopsies for measurements of interleukin (IL)-17A, IL-23, IL-6, transforming growth factor-beta (TGF-β), interferon-gamma (IFN-γ), mRNA levels as well as immunohistochemical (IHC) analyses were performed.
The gene expression for all cytokines in UC and for all cytokines except for TGF-β in CD were significantly increased compared with the controls. The immunohistochemical analysis showed significantly increased number of IL-17A positive cells in lamina propria and epithelium of both UC and CD compared to controls. The levels of IL-17A and IL-23 mRNA were significantly higher in UC than in CD while the levels of IL-6 were significantly higher in CD compared with UC. The levels of IL-17A, IL-6 and IL-23 mRNA were associated with the disease activity score in both UC and CD. IFN-γ was associated with the disease activity in UC, but did not reach significant level in CD.
Increased levels of IL-17A and IL-23 were found in both UC and CD compared to controls. Association to the grade of inflammation and clinical activity was also observed. IL-17A and IL-23 were significantly higher in UC than in CD. TH1 and TH17 cytokines seem to act synergistically in inflammatory bowel disease (IBD) with no apparent polarization between UC and CD.
克罗恩病(CD)和溃疡性结肠炎(UC)分别与辅助性 T 细胞 1(TH1)和 TH2 细胞因子谱相关。最近,TH17 细胞谱系已经被引入,但其在 CD 和 UC 炎症中的作用尚未完全了解。
描述未经治疗的 CD 和 UC 患者黏膜中指导 TH17 细胞的细胞因子,并研究其与 TH1 细胞的相互作用。
纳入 79 例未经治疗的 UC 患者、32 例未经治疗的 CD 患者和 23 例无结肠疾病迹象的对照者。评估溃疡性结肠炎(UCDAI)和克罗恩病(CDAI)的临床指标。进行白细胞介素(IL)-17A、IL-23、IL-6、转化生长因子-β(TGF-β)、干扰素-γ(IFN-γ)mRNA 水平的测量以及免疫组织化学(IHC)分析。
与对照组相比,UC 中所有细胞因子的基因表达以及 CD 中除 TGF-β 外的所有细胞因子的基因表达均显著增加。免疫组织化学分析显示,UC 和 CD 的固有层和上皮中 IL-17A 阳性细胞的数量显著增加。与 CD 相比,UC 中 IL-17A 和 IL-23 mRNA 的水平显著升高,而 CD 中 IL-6 的水平显著升高。UC 和 CD 中 IL-17A、IL-6 和 IL-23 mRNA 的水平与疾病活动评分相关。IFN-γ与 UC 中的疾病活动相关,但在 CD 中未达到显著水平。
与对照组相比,UC 和 CD 中均发现 IL-17A 和 IL-23 水平升高。观察到与炎症程度和临床活动的相关性。UC 中 IL-17A 和 IL-23 显著高于 CD。TH1 和 TH17 细胞因子似乎在炎症性肠病(IBD)中协同作用,UC 和 CD 之间没有明显的极化。