Interleukin 16 is up-regulated in Crohn's disease and participates in TNBS colitis in mice
Interleukin 16 is up-regulated in Crohn's disease and participates in TNBS colitis in mice
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DOI：
10.1053/gast.2000.18164
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发表时间：
2000-10-01
期刊：
影响因子：
29.4
通讯作者：
Kelly, CP
中科院分区：
文献类型：
--
作者：
Keates, AC;Castagliuolo, I;Kelly, CP
背景与目的：白细胞介素16(IL-16)是一种T淋巴细胞来源的细胞因子，它以CD4为受体，选择性地募集携带CD4的细胞。CD4(+)T细胞的渗入是克罗恩病的一个特征；然而，IL-16在肠道炎症中的作用尚不清楚。本研究的目的是确定IL-16在炎症性肠病中的产生是否增加，以及IL-16是否参与了三硝基苯磺酸(TNBS)诱导的小鼠结肠炎。方法：采用逆转录聚合酶链式反应和酶联免疫吸附试验检测炎症性肠病组织中IL-16信使RNA和蛋白水平。C57BL/6或BALB/c小鼠分别用赋形剂、TNBS单独、TNBS+抗IL-16单抗、TNBS+对照单抗处理，或不处理。术后3d或10d评价结肠损伤及炎症反应。结果：克罗恩病患者的结肠IL-16蛋白水平升高(P<；0.05)，但溃疡性结肠炎患者的IL-16蛋白水平无明显变化。抗IL-16单抗治疗显著降低了TNBS诱导的体重减轻(P<；0.001)、粘膜溃疡(P<；0.001)和髓过氧化物酶活性(P<；0.001)，以及TNBS介导的IL-1β和肿瘤坏死因子α水平的升高(P<；0.01)。结论：抗IL-16单抗可减轻TNBS诱导的小鼠结肠损伤和炎症反应。克罗恩病患者结肠黏膜IL-16水平升高，提示IL-16在炎症性肠病的病理生理学中起作用。
Background & Aims: Interleukin (IL)-16 is a T lymphocyte-derived cytokine that uses CD4 as its receptor and hence selectively recruits CD4-bearing cells. Infiltrating CD4(+) T cells are a feature of Crohn's disease; however, the role of IL-16 in intestinal inflammation is unknown. The aim of this study was to determine whether IL-16 production is increased in inflammatory bowel disease and whether IL-16 participates in trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Methods: IL-16 messenger RNA and protein levels in inflammatory bowel disease tissues were determined by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. C57BL/6 or BALB/c mice were treated with vehicle, TNBS alone, TNBS + anti-IL-16 monoclonal antibody (mAb), TNBS + control mAb, or were untreated. Colonic injury and inflammation were evaluated after 3 or 10 days. Results: Colonic IL-16 protein levels were increased in patients with Crohn's disease (P < 0.05) but not ulcerative colitis. Anti-IL-16 mAb treatment significantly reduced TNBS-induced weight loss (P < 0.001), mucosal ulceration (P < 0.05), myeloperoxidase activity (P < 0.001), and TNBS-mediated increases in mucosal levels of IL-1 beta (P < 0.05) and tumor necrosis factor alpha (P < 0.01). Conclusions: Anti-IL-16 mAb reduced colonic injury and inflammation induced by TNBS in mice. Colonic mucosal IL-16 levels were elevated in Crohn's disease, suggesting a role for IL-16 in the pathophysiology of inflammatory bowel disease.