The study for the effects of anti-cytokine therapy on the fibrosis of colon with Cohn disease

抗细胞因子治疗对Cohn病结肠纤维化影响的研究

• 批准号: 14570522
• 负责人: ARISAWA Tobias
• 金额: $ 2.18万
• 依托单位: Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570522/
• 关键词: Crohn disease; anti-cytokine therapy; fibrosis; TGF-β; MMP; 抗TNF療法; 腸管線維化

We studied the effects of anti-TNF antibody (Infliximab) treatment on the fibrosis of colon with Crohn disease. Five patients (male 4 and female 1) with Infliximab treatment were studied. The biopsy specimens were obtained by colonoscopy before and 4 weeks after the treatment. One part of specimens were incubated in DMEM for 24 hours at 37℃. Soluble collagen and total protein concentration in supernatant were measured by ELISA. The other specimens were stored at -80℃ and later mRNAs of TGF (Tumor Growth Factor)-β family and MMP (matrix metalloproteinase) family were assessed by RT-PCR. In all patients, serum CRP level was decreased, longitudinal ulcers were reepithelized and CDAI value was decreased after Infliximab treatment. The release of Soluble collagen was slightly increased after Infliximab treatment, but not significant. The expression of TGF-β 1 was increased in 2 cases and that of TGF-β 3 was also increased in all cases after Infliximab treatment. The expression of MMP-1 was increased in 1 case and that of MMP-12 was decreased in 2 cases. The expression of TGF-β2 was not detected and that of MMP-3 could be detected in 2 cases but not fluctuated.In conclusion, it was suspected that fibrosis of colon with Crohn disease is stimulated by the expression of TGF family resulted from rapid suppression of inflammation after Infliximab treatment.

我们研究了抗肿瘤坏死因子抗体（英夫利西单抗）治疗克罗恩病结肠纤维化的作用。研究了5例接受英夫利西单抗治疗的患者（男性4例，女性1例）。治疗前及治疗后4周分别行结肠镜检查。将一部分标本在37℃下在DMEM中培养24小时。ELISA法测定上清液中可溶性胶原和总蛋白的浓度。其余标本保存于-80℃，用RT-PCR检测TGF-β家族和MMP家族的mRNA。在所有患者中，血清CRP水平降低，纵向溃疡上皮再生和CDAI值降低英夫利昔单抗治疗后。英夫利西单抗治疗后可溶性胶原蛋白的释放略有增加，但不显著。2例患者治疗后TGF-β 1表达增强，所有患者治疗后TGF-β 3表达均增强。1例MMP-1表达增强，2例MMP-12表达减弱。TGF-β2表达阴性，2例MMP-3表达阳性，但无波动性，提示克罗恩病结肠纤维化可能是因英夫利西单抗治疗后炎症迅速抑制而导致TGF-β 2家族表达增加所致。