Reddy Krishna P, Markowitz Jonathan E, Ruchelli Eduardo D, Baldassano Robert N, Brown Kurt A
Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Dig Dis Sci. 2007 Feb;52(2):365-72. doi: 10.1007/s10620-006-9322-y. Epub 2007 Jan 12.
Dysregulation of interleukin-8 (IL-8) production has been proposed to contribute to intestinal inflammation in inflammatory bowel disease (IBD) patients. Previous studies, which evaluate adult patients with long-standing or steroid-modulated disease, have reported conflicting results regarding the role of IL-8 in IBD pathogenesis. The present study evaluates IL-8 in colonic organ cultures and sera of newly and previously diagnosed pediatric IBD patients with various degrees of histopathologic activity. Colon and terminal ileum biopsies were obtained from 26 patients with Crohn's disease, 12 with ulcerative colitis, 4 with indeterminate colitis, and 12 age-matched normal controls. IBD patients were additionally characterized as newly or previously diagnosed. Supernatants from organ-cultured lamina propria biopsies and sera were evaluated by ELISA for IL-8 protein. IL-8 increased with degree of histologic inflammation regardless of diagnosis (no pathologic diagnosis, 62.6 ng/ml, interquartile range [IQR] 30.4-94.6 ng/ml; mild, 92.0 ng/ml, IQR 21.9-170.0 ng/ml; moderate, 676.2 ng/ml, IQR 46.4-2967.7 ng/ml; severe, 585.6 ng/ml, IQR 149.7-1602.2 ng/ml; P < 0.01). Lamina propria IL-8 was significantly elevated in moderately and severely inflamed tissue segments (603.26 ng/ml; IQR, 72.15-2240.4 ng/ml) compared to noninflamed and mildly inflamed segments (67.70 ng/ml; IQR, 30.38-124.1 ng/ml; P = 0.0009). There was no significant trend in IL-8 concentration when compared by clinical diagnosis. No significant difference was found in IL-8 concentrations in organ cultures from newly diagnosed patients versus those from previously diagnosed patients. There was no significant correlation between serum IL-8 concentration and organ culture IL-8 concentration. We conclude that higher concentrations of IL-8 are found in more histologically inflamed tissue segments from pediatric IBD patients. IL-8 does not appear to be associated with clinical IBD subtype. IL-8 appears to be an integral part of both early and established mucosal inflammation in pediatric IBD patients. These findings suggest that IL-8-specific therapies may universally modify inflammatory activity in IBD patients.
白细胞介素-8（IL-8）产生失调被认为与炎症性肠病（IBD）患者的肠道炎症有关。以往评估成年长期或激素调节疾病患者的研究，在IL-8在IBD发病机制中的作用方面报告了相互矛盾的结果。本研究评估了新诊断和既往诊断的不同组织病理学活动程度的儿科IBD患者的结肠器官培养物和血清中的IL-8。从26例克罗恩病患者、12例溃疡性结肠炎患者、4例不确定性结肠炎患者和12例年龄匹配的正常对照者获取结肠和回肠末端活检组织。IBD患者还被分为新诊断或既往诊断。通过ELISA评估器官培养的固有层活检组织和血清中的上清液中的IL-8蛋白。无论诊断如何，IL-8均随组织学炎症程度增加（无病理诊断，62.6 ng/ml，四分位间距[IQR] 30.4 - 94.6 ng/ml；轻度，92.0 ng/ml，IQR 21.9 - 170.0 ng/ml；中度，676.2 ng/ml，IQR 46.4 - 2967.7 ng/ml；重度，585.6 ng/ml，IQR 149.7 - 1602.2 ng/ml；P < 0.01）。与非炎症和轻度炎症节段（67.70 ng/ml；IQR，30.38 - 124.1 ng/ml；P = 0.0009）相比，固有层IL-8在中度和重度炎症组织节段中显著升高（603.26 ng/ml；IQR，72.15 - 2240.4 ng/ml）。按临床诊断比较时，IL-8浓度无显著趋势。新诊断患者与既往诊断患者的器官培养物中的IL-8浓度无显著差异。血清IL-8浓度与器官培养物IL-8浓度之间无显著相关性。我们得出结论，在儿科IBD患者组织学炎症更严重的组织节段中发现IL-8浓度更高。IL-8似乎与临床IBD亚型无关。IL-8似乎是儿科IBD患者早期和已确立的黏膜炎症的一个组成部分。这些发现表明，IL-8特异性疗法可能普遍改变IBD患者的炎症活动。
