Therapeutic effect of urocortin and adrenomedullin in a murine model of Crohn's disease
Therapeutic effect of urocortin and adrenomedullin in a murine model of Crohn's disease
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DOI：
10.1136/gut.2005.084525
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发表时间：
2006-06-01
期刊：
影响因子：
24.5
通讯作者：
Delgado, M.
中科院分区：
文献类型：
--
作者：
Gonzalez-Rey, E.;Fernandez-Martin, A.;Delgado, M.
背景和目标：尿皮质素1（UCN）和肾上腺髓质素（AM）是最近发现的两种神经肽，由于它们在免疫细胞中的分布和与受体的结合，已经成为潜在的内源性抗炎因子。克罗恩病是一种慢性衰弱性疾病，其特征在于Th1驱动的胃肠道严重炎症。本研究探讨了UCN和AM在小鼠colis.Methods和Results模型中的治疗效果：用UCN或AM治疗显著改善了炎症性结肠炎的临床和组织病理学严重程度，消除了体重减轻，腹泻和炎症，并增加了结肠炎小鼠的存活率。治疗效果与炎症和Th1驱动的自身免疫反应的下调相关，包括对广谱炎症介质的调节。此外，部分参与白细胞介素10分泌的调节细胞在这种治疗效果被证明。重要的是，UCN或AM治疗是治疗有效的，在建立结肠炎和避免复发的diseases.Conclusions：这项工作确定UCN和AM作为两个强大的抗炎因子的能力，以灭活肠道炎症反应和恢复粘膜免疫耐受在多个层次。因此，这两种肽代表了用于治疗克罗恩病和其他Th1介导的炎性疾病的新的多步骤治疗方法。
Background and aim: Urocortin 1 (UCN) and adrenomedullin (AM) are two recently discovered neuropeptides that, due to their distribution and binding to receptors in immune cells, have emerged as potential endogenous anti-inflammatory factors. Crohn's disease is a chronic debilitating disease characterised by a Th1 driven severe inflammation of the gastrointestinal tract. This study investigated the therapeutic effect of UCN and AM in a murine model of colitis.Methods and results: Treatment with UCN or AM ameliorated significantly the clinical and histopathological severity of the inflammatory colitis, abrogating body weight loss, diarrhoea, and inflammation, and increased the survival rate of colitic mice. The therapeutic effect was associated with downregulation of both inflammatory and Th1 driven autoimmune responses, including regulation of a wide spectrum of inflammatory mediators. In addition, partial involvement of interleukin 10 secreting regulatory cells in this therapeutic effect was demonstrated. Importantly, UCN or AM treatments were therapeutically effective in established colitis and avoided recurrence of the disease.Conclusions: This work identifies UCN and AM as two potent anti-inflammatory factors with the capacity to deactivate the intestinal inflammatory response and restore mucosal immune tolerance at multiple levels. Consequently, both peptides represent novel multistep therapeutic approaches for the treatment of Crohn's disease and other Th1 mediated inflammatory diseases.