Katz Lior H, Kopylov Uri, Fudim Ella, Yavzori Miri, Picard Orit, Ungar Bella, Eliakim Rami, Ben-Horin Shomron, Chowers Yehuda
Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
Clin Res Hepatol Gastroenterol. 2014 Sep;38(4):491-8. doi: 10.1016/j.clinre.2014.01.010. Epub 2014 Mar 5.
The T cell cytokine IL-17 and the Th-17 pathway appear to have a role in the pathogenesis of inflammatory bowel diseases. IL-2 is a potent stimulator of lymphocyte proliferation and IL2/IL21 receptor polymorphisms have recently been associated with susceptibility to IBD.
To evaluate the expression of IL-17, IL-2 and TNFα in Crohn's disease (CD) patients with and without anti-TNFs.
Cytokine expression was evaluated by ELISA and intracellular staining of CD4(+) T-cells from the peripheral blood and lamina propria of CD patients and of non-IBD controls. The results were stratified by disease activity and anti-TNF treatment.
IL2 expression was significantly elevated in CD patients not treated with anti-TNFs in comparison to healthy controls (19.6% vs. 33.3%, P=0.03) and CD patients treated with anti-TNFs (20.4% vs. 33.3%, P=0.02), and similar in infliximab-treated patients and controls. IL17 expression was similar in CD patients and controls, and was not affected by anti-TNF therapy. TNFα expression in patients with active CD was increased compared to controls (35.5% vs 25.7%, P<0.005), and was significantly decreased in anti-TNF treated patients in comparison to CD patients without anti-TNFs (39.6% vs 26.2%, P=0.01).
Expression of IL2 was significantly decreased in anti-TNF-treated CD patients in comparison to non-treated CD patients and controls. This novel finding may indicate a further mechanism of anti-TNF therapy in CD. Expression of IL17 was not influenced by presence of CD or anti-TNF therapy, which may partly explain the failure of recent clinical trials investigating anti-IL17 therapy in CD.
T细胞细胞因子白细胞介素-17（IL-17）和Th17通路似乎在炎症性肠病的发病机制中起作用。白细胞介素-2（IL-2）是淋巴细胞增殖的有效刺激物，IL2/IL21受体多态性最近与炎症性肠病的易感性相关。
评估使用和未使用抗TNF药物的克罗恩病（CD）患者中IL-17、IL-2和肿瘤坏死因子α（TNFα）的表达。
通过酶联免疫吸附测定（ELISA）以及对CD患者和非炎症性肠病（IBD）对照者外周血和固有层中CD4(+) T细胞进行细胞内染色来评估细胞因子表达。结果按疾病活动度和抗TNF治疗进行分层。
与健康对照者（19.6%对33.3%，P=0.03）和接受抗TNF治疗的CD患者（20.4%对33.3%，P=0.02）相比，未接受抗TNF治疗的CD患者中IL2表达显著升高，且在接受英夫利昔单抗治疗的患者和对照者中相似。CD患者和对照者中IL17表达相似，且不受抗TNF治疗影响。与对照者相比，活动期CD患者中TNFα表达增加（35.5%对25.7%，P<0.005），与未使用抗TNF药物的CD患者相比，接受抗TNF治疗的患者中TNFα表达显著降低（39.6%对26.2%，P=0.01）。
与未治疗的CD患者和对照者相比，接受抗TNF治疗的CD患者中IL2表达显著降低。这一新发现可能表明抗TNF治疗在CD中的另一种机制。IL17表达不受CD存在或抗TNF治疗影响，这可能部分解释了近期研究抗IL17治疗CD的临床试验失败的原因。
