Lindsay J, Van Montfrans C, Brennan F, Van Deventer S, Drillenburg P, Hodgson H, Te Velde A, Sol Rodriguez Pena M
The Kennedy Institute of Rheumatology, Imperial College School of Medicine, London, UK.
Gene Ther. 2002 Dec;9(24):1715-21. doi: 10.1038/sj.gt.3301841.
The transfer of genes encoding immunomodulatory proteins to the intestinal mucosa is a promising new approach to the treatment of Crohn's disease (CD). This study investigates the therapeutic efficacy of an adenoviral vector encoding IL-10 (AdvmuIL-10) in experimental colitis. BALB/c mice were treated with a single intravenous injection of AdvmuIL-10, empty cassette virus (Adv0) or PBS prior to the induction of trinitrobenzene sulphonic acid (TNBS) colitis. AdvmuIL-10 treatment prevented the severe loss of body weight associated with TNBS administration. In addition, AdvmuIL-10 therapy led to a significant reduction in both stool markers of inflammation (IL-1beta and TNFR-II) and acute phase response (serum amyloid protein). Finally, the histological scores of mice with TNBS colitis treated with AdvmuIL-10 were significantly lower than Adv0- or PBS-treated controls. The therapeutic efficacy of AdvmuIL-10 was associated with a decrease in the IFN-gamma and IL-6 levels detected in colonic homogenates from mice with TNBS colitis, whereas no effect was observed on cytokine release from stimulated systemic lymphocytes. Thus, AdvmuIL-10 is an effective therapy in the TNBS model of colitis. Gene therapy strategies using adenoviral vectors encoding IL-10 may prove to be a potent therapy for chronic inflammatory conditions such as CD.
将编码免疫调节蛋白的基因转移至肠道黏膜是治疗克罗恩病（CD）的一种有前景的新方法。本研究调查了编码白细胞介素-10的腺病毒载体（AdvmuIL-10）在实验性结肠炎中的治疗效果。在诱导三硝基苯磺酸（TNBS）结肠炎之前，对BALB/c小鼠单次静脉注射AdvmuIL-10、空载体病毒（Adv0）或磷酸盐缓冲液（PBS）。AdvmuIL-10治疗可防止与TNBS给药相关的严重体重减轻。此外，AdvmuIL-10治疗导致炎症的粪便标志物（白细胞介素-1β和肿瘤坏死因子受体-II）和急性期反应（血清淀粉样蛋白）均显著降低。最后，用AdvmuIL-10治疗的TNBS结肠炎小鼠的组织学评分显著低于Adv0或PBS治疗的对照组。AdvmuIL-10的治疗效果与TNBS结肠炎小鼠结肠匀浆中检测到的干扰素-γ和白细胞介素-6水平降低有关，而对刺激的全身淋巴细胞释放细胞因子未观察到影响。因此，AdvmuIL-10在TNBS结肠炎模型中是一种有效的治疗方法。使用编码白细胞介素-10的腺病毒载体的基因治疗策略可能被证明是治疗诸如CD等慢性炎症性疾病的有效疗法。
