Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Therap Adv Gastroenterol. 2010 Jan;3(1):23-30. doi: 10.1177/1756283X09351733.
The pathogenesis of Crohn's disease involves an immune-mediated damage to the gut mucosa. Current developed therapies are based on the use of immunosuppressive drugs that can lead to significant drug-related adverse responses. There is a need for a therapeutic strategy that is more specific and less global in its effect on the immune system. Oral tolerance is an active process wherein oral administration of antigens is associated with the induction of regulatory cells and the suppression of effector cells directed toward specific and nonspecific antigens. Studies in animal models of experimental colitis suggest that oral administration of proteins extracted from the gut can induce tolerance and alleviate the disease symptoms. Recent clinical trials showed that oral administration of Alequel, an autologous protein-containing colon extract, to patients with Crohn's disease is safe and may be effective as a therapeutic modality for treating the disease. This treatment was associated with disease-associated antigen alterations of the immune response in the patients. Oral administration of Alequel could provide a patient-tailored approach that is side-effect-free for the treatment of patients with Crohn's disease.
克罗恩病的发病机制涉及免疫介导的肠道黏膜损伤。目前开发的治疗方法基于使用免疫抑制剂,这些药物可能会导致严重的药物相关不良反应。因此,需要一种更具特异性、对免疫系统影响更小的治疗策略。口服耐受是一种主动过程,其中口服给予抗原与诱导调节细胞和抑制针对特定和非特定抗原的效应细胞有关。实验性结肠炎动物模型的研究表明,口服给予从肠道提取的蛋白质可以诱导耐受并缓解疾病症状。最近的临床试验表明,给克罗恩病患者口服 Alequel(一种含有自体蛋白的结肠提取物)是安全的,并且可能作为治疗这种疾病的一种治疗方式是有效的。这种治疗与患者免疫反应中与疾病相关的抗原改变有关。Alequel 的口服给药可以为克罗恩病患者提供一种针对患者的、无副作用的治疗方法。