Griga T, Hebler U, Voigt E, Tromm A, May B
Department of Gastroenterology, University Hospital Bergmannsheil, Bürkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany.
Hepatogastroenterology. 2000 Nov-Dec;47(36):1604-7.
BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF), a potent angiogenic, permeability-enhancing cytokine plays an important role in tissue repair and chronic inflammatory disorders. Peripheral blood mononuclear cells (PBMCs) and the inflamed mucosa have been demonstrated to be main sources of the recently described circulating VEGF in patients with inflammatory bowel disease (IBD). There is no current information about the influence of immunoregulatory cytokines on VEGF in IBD. The present study examines the effect of interleukin-4 on the increased VEGF production of PBMCs in patients with IBD.
Unstimulated PBMCs from 17 patients with Crohn's disease, 16 patients with ulcerative colitis and 8 healthy controls were cultured with or without IL-4. VEGF production was measured in the supernatant using an enzyme-linked immunosorbent assay.
IL-4 led to a significant reduction of the VEGF production by PBMCs of both active Crohn's disease patients (471.7 +/- 377.5 pg/mL vs. 208.2 +/- 123.2 pg/mL, P = 0.018, n = 7) and active ulcerative colitis patients (177.1 +/- 79.4 pg/mL vs. 87.4 +/- 77.2 pg/mL, P = 0.008, n = 9). IL-4 inhibited significantly the VEGF production by PBMCs of patients with inactive Crohn's disease (179.2 +/- 133.9 pg/mL vs. 87.7 +/- 56.6 pg/mL, P = 0.005, n = 10). There was no significant difference of VEGF release by PBMCs cultured with IL-4 in patients with active Crohn's disease or active ulcerative colitis compared with PBMCs cultured without IL-4 in patients with inactive disease and healthy controls (112.6 +/- 41.9 pg/mL, n = 8).
IL-4 has been shown to reduce the increased VEGF production of PBMCs in patients with IBD to normal levels. The known defective immunosuppressive effect of IL-4 in IBD may contribute to the pathogenic cascade leading to inflammation by VEGF mediated mechanisms.
背景/目的：血管内皮生长因子（VEGF）是一种强效的促血管生成、增强通透性的细胞因子，在组织修复和慢性炎症性疾病中发挥重要作用。外周血单核细胞（PBMCs）和炎症黏膜已被证明是炎症性肠病（IBD）患者中最近描述的循环VEGF的主要来源。目前尚无关于免疫调节细胞因子对IBD中VEGF影响的信息。本研究探讨白细胞介素-4对IBD患者PBMCs中VEGF产生增加的影响。
将17例克罗恩病患者、16例溃疡性结肠炎患者和8例健康对照者的未刺激PBMCs在有或无IL-4的情况下进行培养。使用酶联免疫吸附测定法测量上清液中的VEGF产生。
IL-4导致活动期克罗恩病患者（471.7±377.5 pg/mL对208.2±123.2 pg/mL，P = 0.018，n = 7）和活动期溃疡性结肠炎患者（177.1±79.4 pg/mL对87.4±77.2 pg/mL，P = 0.008，n = 9）的PBMCs中VEGF产生显著降低。IL-4显著抑制非活动期克罗恩病患者（179.2±133.9 pg/mL对87.7±56.6 pg/mL，P = 0.005，n = 10）的PBMCs中VEGF产生。与非活动期疾病患者和健康对照者中未用IL-4培养的PBMCs相比，活动期克罗恩病或活动期溃疡性结肠炎患者中用IL-4培养的PBMCs的VEGF释放无显著差异（112.6±41.9 pg/mL，n = 8）。
已证明IL-4可将IBD患者PBMCs中增加的VEGF产生降低至正常水平。IBD中已知的IL-4免疫抑制作用缺陷可能导致通过VEGF介导的机制引发炎症的致病级联反应。
