Gay Jérôme, Kokkotou Efi, O'Brien Michael, Pothoulakis Charalabos, Karalis Katia P
Division of Endocrinology, Children's Hospital, Boston, MA, USA.
Neuroimmunomodulation. 2006;13(2):114-21. doi: 10.1159/000096656. Epub 2006 Oct 14.
Interleukin (IL)-6 is a proinflammatory cytokine implicated in the pathogenesis of inflammatory bowel disease. IL-6 is locally upregulated in inflammatory bowel disease patients and in murine models of experimental colitis. Treatment with anti-IL-6 receptor antibody ameliorates intestinal inflammation.
It was the aim of this study to investigate the role of genetic IL-6 deficiency in trinitrobenzene sulfonic acid (TNBS)-mediated colitis, an experimental model inflammation that shares several features with Crohn's disease in humans.
Acute colitis was induced in wild-type and IL-6-deficient (Il-6(-/-)) mice by intracolonic administration of TNBS. Forty-eight hours after treatment, the local and systemic features of inflammation, i.e. food intake, weight loss, histological markers of colitis, cytokine expression by real-time PCR, food intake and body weight changes, were assessed.
In wild-type mice, TNBS administration increased both IL-6 serum levels and local expression of IL-6 by 36 and 9 fold, respectively, compared with control, vehicle-injected mice. Compared with the wild-type mice, the Il-6(-/-) mice had significantly reduced intestinal inflammation as evidenced by epithelial damage, neutrophil infiltration, colon thickness and proinflammatory cytokine expression, following treatment with TNBS. Moreover, baseline levels of the antiinflammatory cytokines IL-10 and tumor growth factor-beta were significantly elevated in Il-6(-/-)compared with the wild-type mice.
Our results demonstrate that Il-6(-/-)are partially protected from the development of TNBS-induced acute experimental colitis, most likely via their significantly elevated baseline levels of antiinflammatory cytokines.
白细胞介素（IL）-6是一种促炎细胞因子，与炎症性肠病的发病机制有关。在炎症性肠病患者和实验性结肠炎的小鼠模型中，IL-6在局部上调。用抗IL-6受体抗体治疗可改善肠道炎症。
本研究旨在探讨遗传性IL-6缺乏在三硝基苯磺酸（TNBS）介导的结肠炎中的作用，TNBS介导的结肠炎是一种实验性炎症模型，与人类克罗恩病有若干共同特征。
通过结肠内给予TNBS在野生型和IL-6缺陷（Il-6(-/-)）小鼠中诱导急性结肠炎。治疗48小时后，评估炎症的局部和全身特征，即食物摄入量、体重减轻、结肠炎的组织学标志物、通过实时PCR检测的细胞因子表达、食物摄入量和体重变化。
与对照的注射赋形剂小鼠相比，在野生型小鼠中，给予TNBS后IL-6血清水平和IL-6局部表达分别增加了36倍和9倍。与野生型小鼠相比，在用TNBS治疗后，Il-6(-/-)小鼠的肠道炎症明显减轻，表现为上皮损伤、中性粒细胞浸润、结肠厚度和促炎细胞因子表达。此外，与野生型小鼠相比，Il-6(-/-)小鼠中抗炎细胞因子IL-10和肿瘤生长因子-β的基线水平显著升高。
我们的结果表明，Il-6(-/-)小鼠对TNBS诱导的急性实验性结肠炎的发展具有部分保护作用，最可能是通过其显著升高的抗炎细胞因子基线水平实现的。
