Schmidt Carsten, Giese Thomas, Hermann Eva, Zeuzem Stefan, Meuer Stefan C, Stallmach Andreas
Department of Internal Medicine II, Friedrich Schiller-University, Jena, Germany.
Inflamm Bowel Dis. 2007 Jan;13(1):65-70. doi: 10.1002/ibd.20012.
Concentrations of proinflammatory cytokines are increased in the intestinal mucosa of patients with active Crohn's disease (CD). In a prospective study we investigated whether cytokines can predict long-term remission (>6 months) in patients with steroid-refractory CD receiving treatment with infliximab or cyclophosphamide, followed by azathioprine or methotrexate.
Cytokine transcripts were quantified using real-time polymerase chain reaction (PCR) in mucosal biopsies from 19 patients with active, steroid-refractory CD before and 8 weeks after initiation of therapy. Patients were treated with cyclophosphamide (monthly treatment of 750 mg cyclophosphamide intravenously) or infliximab (5 mg/kg body weight) and were followed until relapse of the disease. Statistical analysis was performed to identify predictive factors to discriminate between patients with or without long-term remission.
Seventeen out of 19 patients achieved remission of the disease, two patients were nonresponders, while six out of 17 patients exhibited an early recurrence. Pretreatment TNF-alpha, IL-18, MRP-14, and IL-8 transcripts were significantly correlated with long-term remission. While several cytokines, most importantly MMP-1, determined after 8 weeks were able to predict patients achieving long-term remission, only a decrease of TNF-alpha levels after 8 weeks was predictive. Overall, statistical analysis identified lower pretreatment TNF-alpha levels as the strongest predictor of long-term remission among baseline variables.
Quantification of mucosal TNF-alpha transcripts prior to therapy allows identification of patients achieving long-term remission upon immunosuppression with infliximab or cyclophosphamide. Real-time PCR might have considerable potential in the analysis of disease activity and subsequent clinical management of patients with immunosuppressive therapies.
活动性克罗恩病（CD）患者的肠道黏膜中促炎细胞因子浓度升高。在一项前瞻性研究中，我们调查了细胞因子是否能够预测接受英夫利昔单抗或环磷酰胺治疗，随后使用硫唑嘌呤或甲氨蝶呤的激素难治性CD患者的长期缓解（>6个月）情况。
使用实时聚合酶链反应（PCR）对19例活动性、激素难治性CD患者治疗开始前及治疗8周后的黏膜活检样本中的细胞因子转录本进行定量分析。患者接受环磷酰胺（每月静脉注射750 mg环磷酰胺）或英夫利昔单抗（5 mg/kg体重）治疗，并随访至疾病复发。进行统计分析以确定区分有或无长期缓解患者的预测因素。
19例患者中有17例实现疾病缓解，2例患者无反应，而17例患者中有6例出现早期复发。治疗前肿瘤坏死因子-α（TNF-α）、白细胞介素-18（IL-18）、髓样相关蛋白14（MRP-14）和白细胞介素-8（IL-8）转录本与长期缓解显著相关。虽然8周后测定的几种细胞因子，最重要的是基质金属蛋白酶-1（MMP-1）能够预测实现长期缓解的患者，但只有8周后TNF-α水平的降低具有预测性。总体而言，统计分析确定治疗前较低的TNF-α水平是基线变量中预测长期缓解的最强因素。
治疗前对黏膜TNF-α转录本进行定量分析能够识别出接受英夫利昔单抗或环磷酰胺免疫抑制治疗后实现长期缓解的患者。实时PCR在免疫抑制治疗患者的疾病活动分析及后续临床管理中可能具有相当大的潜力。
