Role of interleukin-6 in bleomycin-induced lung inflammatory changes in mice
Role of interleukin-6 in bleomycin-induced lung inflammatory changes in mice
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DOI：
10.1165/rcmb.2007-0299oc
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发表时间：
2008-05-01
影响因子：
6.4
通讯作者：
Ishizaka, Akitoshi
中科院分区：
文献类型：
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作者：
Saito, Fumitake;Tasaka, Sadatomo;Ishizaka, Akitoshi
白细胞介素-6（IL-6）参与多种炎症性疾病的发病机制，但其在博莱霉素（BLM）诱导的肺损伤和随后的纤维化变化中的作用仍有待确定。我们使用野生型（WT）和IL-6缺陷型（IL-6（-/-））小鼠评估IL-6在BLM诱导的肺部炎症变化中的作用。用lmg/kg BILM对小鼠进行气管内处理，并在2、7或21天后处死。通过支气管肺泡灌洗液（BAL）中的细胞分类计数和肺中的细胞因子水平评估急性期（第2天和第7天）的肺部炎症。在第21天通过组织病理学和胶原测定评价肺纤维化变化。在第2天，BILM给药诱导BAL液中总细胞、巨噬细胞和中性粒细胞数量显著增加，而IL-6（-/-）小鼠中这些数量减少（P < 0.05）。肺病理学还显示炎性细胞积聚，与WT小鼠相比，IL-6（-/-）小鼠中的炎性细胞积聚减弱。在WT小鼠中，分别在BLM激发后2天和7天观察到TGF-β（1）和CCL 3水平升高。在第7天，BLM诱导的炎性细胞积聚在基因型之间没有差异。BILM激发后21天的肺病理学显示显著的纤维化变化，胶原含量增加，这在IL-6（-/-）小鼠中减弱。尽管在第21天，肺中的TGF-β（1）水平在基因型之间没有差异，但IL-6（-/-）小鼠中的CCL 3显著较低。提示IL-6可能在BLM肺损伤及随后的纤维化改变的发病机制中起重要作用。
Interleukin-6 (IL-6) is known to be involved in the pathogenesis of various inflammatory diseases, but its role in bleomycin (BLM)induced lung injury and subsequent fibrotic changes remains to be determined. We evaluated the role of IL-6 in the lung inflammatory changes induced by BLM using wild-type (WT) and IL-6-deficient (IL-6(-/-)) mice. The mice were treated intratracheally with I mg/kg BILM and killed 2, 7, or 21 days later. Lung Inflammation in the acute phase (Days 2 and 7) was assessed by differential cell counts in bronchoalveolar lavage (BAL) fluid and cytokine levels in the lung. Lung fibrotic changes were evaluated on Day 21 by histopathology and Collagen assay. On Day 2, BILM administration induced significant increases in the numbers of total cells, macrophages, and neutrophils in BAL fluid, which were attenuated in IL-6(-/-) mice (P < 0.05). Lung pathology also showed inflammatory cell accumulation, which was attenuated in the IL-6(-/-) mice compared with WT mice. In WT mice, elevated levels of TGF-beta(1) and CCL3 were observed 2 and 7 days after BLM challenge, respectively. On Day 7, BLM-induced inflammatory cell accumulation did not differ between the genotypes. Lung pathology 21 days after BILM challenge revealed significant fibrotic changes with increased Collagen content, which was attenuated in IL-6(-/-) mice. Although the TGF-beta(1) level in the lung did not differ between the genotypes on Day 21, CCL3 was significantly lower in IL-6(-/-) mice. These results indicate that IL-6 may play an important role in the pathogenesis of BLM-incluced lung injury and subsequent fibrotic changes.