Immunomodulatory Effect of Vancomycin on Treg in Pediatric Inflammatory Bowel Disease and Primary Sclerosing Cholangitis
Immunomodulatory Effect of Vancomycin on Treg in Pediatric Inflammatory Bowel Disease and Primary Sclerosing Cholangitis
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DOI：
10.1007/s10875-012-9801-1
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发表时间：
2013-02-01
影响因子：
9.1
通讯作者：
Cox, Kenneth L.
中科院分区：
文献类型：
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作者：
Abarbanel, David N.;Seki, Scott M.;Cox, Kenneth L.
万古霉素已被证明可作为免疫调节剂影响肿瘤坏死因子-α（TNF-α）通路;这被认为与其作为抗生素的功能不同[1]。既往研究表明，口服万古霉素（OV）是治疗儿童原发性硬化性胆管炎（PSC）和炎症性肠病（IBD）的有效方法[2，3]。由于这两种疾病都与免疫功能障碍有关，我们假设万古霉素对IBD和PSC的治疗作用是通过免疫调节实现的。因此，我们研究了14名PSC和IBD儿童在OV治疗期间发生的体内免疫学变化。在OV给药3个月内，外周γ-谷氨酰转肽酶（GGT）和丙氨酸氨基转移酶（ALT）浓度、白色血细胞（WBC）计数和中性粒细胞计数从治疗前的升高水平恢复正常。患者还表现出改善的胆道成像研究，肝活检和IBD症状和活检。此外，血浆转化生长因子β（TGF-β）水平增加，而没有Th 1或Th 2相关细胞因子产生的同时变化。与治疗前水平相比，OV治疗的PSC+ IBD患者中的CD 4 + CD 25 hiCD 127 lo和CD 4 + FoxP 3+调节性T（Treg）细胞的外周水平也增加。一项独特的病例研究表明，OV停药后，OVin治疗PSC+ IBD的疗效并不总是持久，PSC复发与血液Treg水平降低相关;随后的OV再治疗与血液Treg水平升高和肝功能检查（LFT）正常化相关。总之，这些研究支持PSC伴IBD的免疫相关病理生理学，其对OV有反应。
Vancomycin has been shown to affect tumor necrosis factor-alpha (TNF-alpha) pathways as an immunomodulator; this is thought to be separate from its function as an antibiotic [1]. Previous studies have shown that oral vancomycin (OV) is an effective treatment for concomitant primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) in children [2, 3]. Since both diseases are associated with immune dysfunction, we hypothesized that vancomycin's therapeutic effect in IBD and PSC occurs through immunomodulation. Therefore, we examined the in vivo immunological changes that occur during OV treatment of 14 children with PSC and IBD. Within 3 months of OV administration, peripheral gamma-glutamyl transpeptidase (GGT) and alanine aminotransferase (ALT) concentrations, white blood cell (WBC) counts, and neutrophil counts normalized from elevated levels before treatment. Patients also demonstrated improved biliary imaging studies, liver biopsies and IBD symptoms and biopsies. Additionally, plasma transforming growth factor beta (TGF-beta) levels were increased without concurrent shifts in Th1-or Th2-associated cytokine production. Peripheral levels of CD4+CD25hiCD127lo and CD4+FoxP3+ regulatory T (Treg) cells also increased in OV-treated PSC+ IBD patients compared to pretreatment levels. A unique case study shows that the therapeutic effects of OVin the treatment of PSC+ IBD do not always endure after OV discontinuation, with relapse of PSC associated with a decrease in blood Treg levels; subsequent OV retreatment was then associated with a rise in blood Treg levels and normalization of liver function tests (LFTs). Taken together, these studies support immune-related pathophysiology of PSC with IBD, which is responsive to OV.