Isomaltitol Exacerbates Neutrophilia but Reduces Eosinophilia: New Insights into the Sephadex Model of Lung Inflammation
Isomaltitol Exacerbates Neutrophilia but Reduces Eosinophilia: New Insights into the Sephadex Model of Lung Inflammation
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DOI：
10.1159/000321820
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发表时间：
2011-01-01
影响因子：
2.8
通讯作者：
Uppugunduri, Srinivas
中科院分区：
文献类型：
--
作者：
Evaldsson, Chamilly;Ryden, Ingvar;Uppugunduri, Srinivas
工作背景：我们之前已经在体外静态粘附试验中检查了异麦芽糖醇，并有兴趣研究观察到的潜在抗炎作用是否与体内相关。葡聚糖诱导的肺部炎症模型被认为是一个合适的模型，因为在用葡聚糖激发后观察到的整体炎症终点的显著变化。研究方法：将雄性Sprague-Dawley大鼠用Sephadex（5 mg/ml）、媒介物（0.9%NaCl）、异麦芽糖醇（50 mg/ml）或异麦芽糖醇和Sephadex的组合进行气管内滴注。24小时后，将肺称重以测量水肿并保存用于组织学。支气管肺泡灌洗液用于分析肿瘤坏死因子、半胱氨酰白三烯、白细胞分类计数和总计数。结果如下：分类计数表明，异麦芽糖醇增加了中性粒细胞成分，同时减少嗜酸性粒细胞，从而断言通常嗜酸性粒细胞为主的葡聚糖凝胶诱导的细胞概况的调节作用。单独使用异麦芽糖醇也会增加水肿和半胱氨酰白三烯，与葡聚糖凝胶联合使用时通常会加重总炎症。在这项研究中没有调查的机制，但影响可能涉及到异麦芽糖醇的渗透和结构特定的属性的组合。结论：我们的研究结果表明，异麦芽糖醇可以调节葡聚糖凝胶滴注诱导的炎症反应，除了具有促炎作用本身，因此可能会提供新的见解，这种广泛使用的动物模型的机制。类似于异麦芽糖醇的糖醇已经用于帮助囊性纤维化患者的粘液清除，异麦芽糖醇也可能用于此目的。版权所有（C）2010 S. Karger AG，巴塞尔
Background: We have previously examined isomaltitol in an in vitro static adhesion assay and were interested in investigating whether the potentially anti-inflammatory effects observed there could be relevant in vivo. The Sephadex-induced lung inflammation model was considered a suitable model due to the significant changes in global inflammatory endpoints seen upon provocation with Sephadex. Methods: Male Sprague-Dawley rats were instilled intratracheally with Sephadex (5 mg/ml), vehicle (0.9% NaCl), isomaltitol (50 mg/ml) or a combination of isomaltitol and Sephadex. After 24 h, the lungs were weighed to measure edema and preserved for histology. Bronchoalveolar lavage fluid was used for analysis of tumor necrosis factor, cysteinyl leukotrienes, and differential and total leukocyte counts. Results: Differential counts showed that isomaltitol increased the neutrophil component while decreasing the eosinophilia, thus asserting a modulatory role on the usually eosinophil-dominated Sephadex-induced cell profile. Isomaltitol alone also increased edema and cysteinyl leukotrienes, and generally aggravated total inflammation in combination with Sephadex. The mechanisms were not investigated in this study, but effects could relate to a combination of isomaltitol's osmotic and structure-specific properties. Conclusion: Our results show that isomaltitol can modulate the inflammatory response induced by Sephadex instillation in addition to having proinflammatory effects on its own, and may therefore provide new insights into the mechanisms of this widely used animal model. Sugar alcohols similar to isomaltitol have already been used to aid mucus clearance in cystic fibrosis patients, and it is possible that isomaltitol could also be used for this purpose. Copyright (C) 2010 S. Karger AG, Basel