Grottrup-Wolfers E, Moeller J, Karbach U, Muller-Lissner S, Endres S
Virchow-Klinikum, Humboldt-Universitat Berlin, Germany.
Eur J Clin Invest. 1996 Feb;26(2):115-22. doi: 10.1046/j.1365-2362.1996.123262.x.
The aim of this study was to investigate the involvement of the monocyte-derived cytokines interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in idiopathic inflammatory bowel disease. Endoscopic biopsies of normal and inflamed intestinal mucosa were obtained from patients with ulcerative colitis (n = 11) and with Crohn's disease (n = 10). Intestinal mucosal cells were isolated by collagenase digestion. Cell viability, morphology and CD14 expression were determined. To measure cell-associated cytokine levels, cells were lysed and analysed for IL-1beta and TNF-alpha in specific radioimmunoassays and for IL-6 using a biological assay. Compared with mucosal cells from control patients without inflammatory bowel disease the inflamed intestine in ulcerative colitis and Crohn's disease displayed markedly enhanced levels of IL-1beta (median 245 pg 10(-6) cells, range 30-1275) and IL-6 (median 22 U 10(-6) cells, range 1-298). Non-inflamed mucosa in patients with ulcerative colitis and Crohn's disease did not show elevated levels of IL-1beta (median 50 pg 10(-6) cells, range 33-90) or IL-6 (mean below detection limit of assay, i.e. 1 U 10(-6) cells). In contrast, no clear cut difference between inflamed and non-inflamed mucosa could be detected for TNF-alpha. High tissue levels of IL-6 were associated with a high endoscopic grade of local inflammation. These results suggest that the monocyte-derived cytokines IL-1beta and IL-6 are mediators of inflammation in inflammatory bowel disease.
本研究的目的是调查单核细胞衍生的细胞因子白细胞介素1β(IL-1β)、白细胞介素6(IL-6)和肿瘤坏死因子-α(TNF-α)在特发性炎症性肠病中的作用。从溃疡性结肠炎患者(n = 11)和克罗恩病患者(n = 10)获取正常和发炎肠黏膜的内镜活检样本。通过胶原酶消化分离肠黏膜细胞。测定细胞活力、形态和CD14表达。为测量细胞相关细胞因子水平,裂解细胞并通过特异性放射免疫测定法分析IL-1β和TNF-α,使用生物测定法分析IL-6。与无炎症性肠病的对照患者的黏膜细胞相比,溃疡性结肠炎和克罗恩病发炎肠段中IL-1β(中位数245 pg 10⁻⁶细胞,范围30 - 1275)和IL-6(中位数22 U 10⁻⁶细胞,范围1 - 298)水平显著升高。溃疡性结肠炎和克罗恩病患者的非发炎黏膜中IL-1β(中位数50 pg 10⁻⁶细胞,范围33 - 90)或IL-6(平均低于检测限,即1 U 10⁻⁶细胞)未显示升高。相比之下,TNF-α在发炎和未发炎黏膜之间未检测到明显差异。高组织水平的IL-6与局部炎症的高内镜分级相关。这些结果表明,单核细胞衍生的细胞因子IL-1β和IL-6是炎症性肠病中炎症的介质。